Medicine by Design / en U of T researchers' approach to producing neural cells could yield new treatments for Parkinson’s /news/u-t-researchers-approach-producing-neural-cells-could-yield-new-treatments-parkinson-s <span class="field field--name-title field--type-string field--label-hidden">U of T researchers' approach to producing neural cells could yield new treatments for Parkinson’s</span> <div class="field field--name-field-featured-picture field--type-image field--label-hidden field__item"> <img loading="eager" srcset="/sites/default/files/styles/news_banner_370/public/2024-05/Andy-Yang-and-Stephane-Angers-crop.jpg?h=062762c7&amp;itok=LwN6tW3B 370w, /sites/default/files/styles/news_banner_740/public/2024-05/Andy-Yang-and-Stephane-Angers-crop.jpg?h=062762c7&amp;itok=0VrvqorZ 740w, /sites/default/files/styles/news_banner_1110/public/2024-05/Andy-Yang-and-Stephane-Angers-crop.jpg?h=062762c7&amp;itok=6JaZuBzT 1110w" sizes="(min-width:1200px) 1110px, (max-width: 1199px) 80vw, (max-width: 767px) 90vw, (max-width: 575px) 95vw" width="740" height="494" src="/sites/default/files/styles/news_banner_370/public/2024-05/Andy-Yang-and-Stephane-Angers-crop.jpg?h=062762c7&amp;itok=LwN6tW3B" alt="&quot;&quot;"> </div> <span class="field field--name-uid field--type-entity-reference field--label-hidden"><span>rahul.kalvapalle</span></span> <span class="field field--name-created field--type-created field--label-hidden"><time datetime="2024-05-13T09:03:19-04:00" title="Monday, May 13, 2024 - 09:03" class="datetime">Mon, 05/13/2024 - 09:03</time> </span> <div class="clearfix text-formatted field field--name-field-cutline-long field--type-text-long field--label-above"> <div class="field__label">Cutline</div> <div class="field__item"><p><em>PhD Student Andy Yang, left, and Professor Stephane Angers, right, at the&nbsp;Donnelly Centre for Cellular and Molecular Biology are advancing a novel approach to developing dopaminergic neurons (supplied images)</em></p> </div> </div> <div class="field field--name-field-author-reporters field--type-entity-reference field--label-hidden field__items"> <div class="field__item"><a href="/news/authors-reporters/anika-hazra" hreflang="en">Anika Hazra</a></div> </div> <div class="field field--name-field-topic field--type-entity-reference field--label-above"> <div class="field__label">Topic</div> <div class="field__item"><a href="/news/topics/breaking-research" hreflang="en">Breaking Research</a></div> </div> <div class="field field--name-field-story-tags field--type-entity-reference field--label-hidden field__items"> <div class="field__item"><a href="/news/tags/institutional-strategic-initiatives" hreflang="en">Institutional Strategic Initiatives</a></div> <div class="field__item"><a href="/news/tags/temerty-faculty-medicine" hreflang="en">Temerty Faculty of Medicine</a></div> <div class="field__item"><a href="/news/tags/donnelly-centre-cellular-biomolecular-research" hreflang="en">Donnelly Centre for Cellular &amp; Biomolecular Research</a></div> <div class="field__item"><a href="/news/tags/graduate-students" hreflang="en">Graduate Students</a></div> <div class="field__item"><a href="/news/tags/leslie-dan-faculty-pharmacy" hreflang="en">Leslie Dan Faculty of Pharmacy</a></div> <div class="field__item"><a href="/news/tags/medicine-design" hreflang="en">Medicine by Design</a></div> <div class="field__item"><a href="/news/tags/parkinson-s" hreflang="en">Parkinson's</a></div> <div class="field__item"><a href="/news/tags/research-innovation" hreflang="en">Research &amp; Innovation</a></div> </div> <div class="field field--name-field-subheadline field--type-string-long field--label-above"> <div class="field__label">Subheadline</div> <div class="field__item">An antibody was used to selectively activate a receptor in a molecular signalling pathway to develop dopaminergic neurons </div> </div> <div class="clearfix text-formatted field field--name-body field--type-text-with-summary field--label-hidden field__item"><p>Researchers at the Ƶ&nbsp;believe they’ve found a way to better control the generation of key neurons depleted in Parkinson’s disease – suggesting a potentially new approach to addressing a disease with no cure and few effective treatments.</p> <p>In preclinical studies, the researchers used an antibody to selectively activate a receptor in a molecular signalling pathway to develop dopaminergic neurons. These neurons produce dopamine, a neurotransmitter critical to brain health.</p> <p>While researchers around the world have been working to coax stem cells to differentiate into dopaminergic neurons to replace those lost in patients living with Parkinson’s disease, the efforts have so far been hindered in part by an inability to target specific receptors and areas of the brain.</p> <p>“We used synthetic antibodies that we had previously developed to target the Wnt signaling pathway,” said principal investigator&nbsp;<strong>Stephane Angers</strong>, who is director of U of T’s Donnelly Centre for Cellular and Molecular Biology and a professor in the&nbsp;Leslie Dan Faculty of Pharmacy&nbsp;and the&nbsp;Temerty Faculty of Medicine.</p> <p>“We can selectively activate this pathway to direct stem cells in the midbrain to develop into neurons by targeting specific receptors in the pathway. This activation method has not been explored before.”</p> <p>Parkinson’s disease is the second-most common neurological disorder after Alzheimer’s, affecting over 100,000 Canadians. It particularly impacts older men, progressively impairing movement and causing pain as well as sleep and mental health issues.</p> <p>Most previous research efforts to activate the Wnt signaling pathway relied on a GSK3 enzyme inhibitor. This method involves multiple signaling pathways for stem cell proliferation and differentiation, which can have an unintended effect on the newly produced neurons and activate off-target cells.</p> <p>“We developed an efficient method for stimulating stem cell differentiation to produce neural cells in the midbrain,” said&nbsp;<strong>Andy&nbsp;Yang</strong>, first author on the study and a PhD student at the Donnelly Centre. “Moreover, cells activated via the FZD5 receptor closely resemble dopaminergic neurons of natural origin.”</p> <p>Another promising finding of the study, <a href="https://journals.biologists.com/dev/article/151/5/dev202545/344080/Exploiting-spatiotemporal-regulation-of-FZD5">published recently in the journal&nbsp;</a><em><a href="https://journals.biologists.com/dev/article/151/5/dev202545/344080/Exploiting-spatiotemporal-regulation-of-FZD5" target="_blank">Development</a>,</em>&nbsp;is that implanting the artificially-produced neurons in a rodent model with Parkinson’s disease led to improvement of the rodent’s locomotive impairment.</p> <p>“Our next step would be to continue using rodent or other suitable models to compare the outcomes of activating the FZD5 receptor and inhibiting GSK3,” said Yang. “These experiments will confirm which method is more effective in improving symptoms of Parkinson’s disease ahead of clinical trials.”</p> <p>The research was supported by U of T’s Medicine by Design program, an <a href="https://isi.utoronto.ca">institutional strategic initiative</a> that receives funding from the Canada First Research Excellence Fund and the Canadian Institutes of Health Research.</p> </div> <div class="field field--name-field-news-home-page-banner field--type-boolean field--label-above"> <div class="field__label">News home page banner</div> <div class="field__item">Off</div> </div> Mon, 13 May 2024 13:03:19 +0000 rahul.kalvapalle 307839 at Medicine by Design, CCRM launch alliance to bolster Canada’s leading position in regenerative medicine /news/medicine-design-ccrm-launch-alliance-bolster-canada-s-leading-position-regenerative-medicine <span class="field field--name-title field--type-string field--label-hidden">Medicine by Design, CCRM launch alliance to bolster Canada’s leading position in regenerative medicine </span> <div class="field field--name-field-featured-picture field--type-image field--label-hidden field__item"> <img loading="eager" srcset="/sites/default/files/styles/news_banner_370/public/2023-12/GettyImages-1737809925-crop.jpg?h=afdc3185&amp;itok=oZqsRTsI 370w, /sites/default/files/styles/news_banner_740/public/2023-12/GettyImages-1737809925-crop.jpg?h=afdc3185&amp;itok=lLct7JVr 740w, /sites/default/files/styles/news_banner_1110/public/2023-12/GettyImages-1737809925-crop.jpg?h=afdc3185&amp;itok=gVPXI2E- 1110w" sizes="(min-width:1200px) 1110px, (max-width: 1199px) 80vw, (max-width: 767px) 90vw, (max-width: 575px) 95vw" width="740" height="494" src="/sites/default/files/styles/news_banner_370/public/2023-12/GettyImages-1737809925-crop.jpg?h=afdc3185&amp;itok=oZqsRTsI" alt="scientist uses a pipette under a fume hood"> </div> <span class="field field--name-uid field--type-entity-reference field--label-hidden"><span>Christopher.Sorensen</span></span> <span class="field field--name-created field--type-created field--label-hidden"><time datetime="2023-12-11T11:35:12-05:00" title="Monday, December 11, 2023 - 11:35" class="datetime">Mon, 12/11/2023 - 11:35</time> </span> <div class="clearfix text-formatted field field--name-field-cutline-long field--type-text-long field--label-above"> <div class="field__label">Cutline</div> <div class="field__item"><p><em>The alliance between Medicine by Design and CCRM aims to create end-to-end capacity from discovery to clinical translation and commercialization (photo by&nbsp;sommersby/Getty Images)</em></p> </div> </div> <div class="field field--name-field-author-reporters field--type-entity-reference field--label-hidden field__items"> <div class="field__item"><a href="/news/authors-reporters/julie-crljen" hreflang="en">Julie Crljen</a></div> </div> <div class="field field--name-field-topic field--type-entity-reference field--label-above"> <div class="field__label">Topic</div> <div class="field__item"><a href="/news/topics/our-community" hreflang="en">Our Community</a></div> </div> <div class="field field--name-field-story-tags field--type-entity-reference field--label-hidden field__items"> <div class="field__item"><a href="/news/tags/institutional-strategic-initiatives" hreflang="en">Institutional Strategic Initiatives</a></div> <div class="field__item"><a href="/news/tags/ccrm" hreflang="en">CCRM</a></div> <div class="field__item"><a href="/news/tags/medicine-design" hreflang="en">Medicine by Design</a></div> </div> <div class="field field--name-field-subheadline field--type-string-long field--label-above"> <div class="field__label">Subheadline</div> <div class="field__item">The partnership will help build a strong pipeline of regenerative medicine technologies and therapies</div> </div> <div class="clearfix text-formatted field field--name-body field--type-text-with-summary field--label-hidden field__item"><p>The Ƶ’s <a href="https://mbd.utoronto.ca/">Medicine by Design</a> initiative and <a href="https://www.ccrm.ca/">CCRM, a non-profit</a> that supports the development and commercialization of regenerative medicines, are launching a new strategic alliance that aims to unlock Toronto’s potential as a world-leading ecosystem for regenerative medicine.</p> <p>The partnership, which was announced at Medicine by Design’s 8th Annual Symposium on Dec. 6, will see the organizations build on their existing strengths in bridging high-risk, high-reward research to industry expertise, biomanufacturing infrastructure and the clinic.</p> <p>The goal of the alliance, whose key members also include the University Health Network (UHN) and U of T, is to create co-ordinated, end-to-end capacity that spans discovery through to clinical translation and commercialization.</p> <p>“Medicine by Design has its deep academic network and track record of supporting world-class research across the&nbsp;Toronto Academic Health Science Network&nbsp;(TAHSN). CCRM has 12 years of success in launching and scaling cell and gene therapy companies at the interface of academia and industry,” said&nbsp;<strong>Allison Brown</strong>, executive director of Medicine by Design.</p> <p>“With this alliance, CCRM is making an investment to sustain Medicine by Design’s discovery programs well into the future. It will enable us to build upon a strong regenerative medicine pipeline of breakthrough technologies and therapies that will ultimately provide health and economic benefits to Canada and the world.”</p> <p><strong>Leah Cowen</strong>, U of T’s vice-president, research and innovation, and strategic initiatives, said the alliance is in keeping with U of T’s strategic plan, and will bring an array of benefits to academic-led innovation.</p> <p>“In addition to the investment into Medicine by Design, for U of T, this partnership unlocks a global network of biomanufacturing expertise, infrastructure and a network of industry partners that expand beyond regenerative medicine – a strategic benefit to the research and clinical communities in Toronto,” said Cowen.</p> <p>Launched in 2015 with the support of a $114-million investment from the&nbsp;Canada First Research Excellence Fund (CFREF), Medicine by Design has made large-scale, strategic investments in high-risk, high-reward research, advancing more than 190 projects. A U of T <a href="https://isi.utoronto.ca/">institutional strategic initiative</a>, it has recruited world-class faculty and provided training programs to thousands of graduate students, post-doctoral fellows and other personnel at U of T and its affiliated hospitals.</p> <p>CCRM, which is funded by the Government of Canada, Province of Ontario and academic and industry partners, has accelerated translation of scientific discovery into new companies and products, with a specific focus on cell and gene therapies.</p> <p><strong>Michael May</strong>, president and CEO of CCRM, said the collaboration will contribute to ensuring that the life-saving potential of regenerative medicine is realized and that a talent pool is developed that will position Canada as a leader in the global cell and gene therapy industry. “Medicine by Design and CCRM, put together, represent an end-to-end perspective of the bench-to-bedside process – research and discovery to company development to manufacturing to bringing the therapy to market,” said May.</p> <p>He noted the alliance will leverage both U of T’s and UHN’s reputations for world-class research and medicine and tap into a network of regenerative medicine-focused faculty and clinicians, as well as experts from the social sciences and other non-STEM fields.</p> <p><strong>Brad Wouters</strong>,&nbsp;executive vice-president, science and research at UHN and a member of Medicine by Design’s executive committee, said the alliance will facilitate access to funding and infrastructure for the clinical translation of new cell and gene therapies being developed by Toronto investigators.</p> <p>“Toronto is known globally for the strength of our stem cell and regenerative medicine accomplishments,” said Wouters, a senior scientist at the Princess Margaret Cancer Centre and professor in the department of medical biophysics in U of T’s Temerty Faculty of Medicine. “UHN is excited to build on our existing partnerships with CCRM through the&nbsp;Centre for Cell and Vector Production&nbsp;and Medicine by Design to support this strategic alliance and its goals to create end-to-end capacity in our ecosystem to create new medicines that will have global patient impact.</p> <p>“From discovery through to clinical validation and manufacturing, we look forward to advancing the next generation of living therapies for our patients.”</p> </div> <div class="field field--name-field-news-home-page-banner field--type-boolean field--label-above"> <div class="field__label">News home page banner</div> <div class="field__item">Off</div> </div> Mon, 11 Dec 2023 16:35:12 +0000 Christopher.Sorensen 304876 at Scientists create ‘cloaked’ donor cell, tissue grafts that escape immune system rejection /news/scientists-create-cloaked-donor-cell-tissue-grafts-escape-immune-system-rejection <span class="field field--name-title field--type-string field--label-hidden">Scientists create ‘cloaked’ donor cell, tissue grafts that escape immune system rejection </span> <div class="field field--name-field-featured-picture field--type-image field--label-hidden field__item"> <img loading="eager" srcset="/sites/default/files/styles/news_banner_370/public/2023-12/Nagy-portrait_larger-crop.jpg?h=afdc3185&amp;itok=0VqGp7HD 370w, /sites/default/files/styles/news_banner_740/public/2023-12/Nagy-portrait_larger-crop.jpg?h=afdc3185&amp;itok=zEOLlteu 740w, /sites/default/files/styles/news_banner_1110/public/2023-12/Nagy-portrait_larger-crop.jpg?h=afdc3185&amp;itok=wh9C7nyJ 1110w" sizes="(min-width:1200px) 1110px, (max-width: 1199px) 80vw, (max-width: 767px) 90vw, (max-width: 575px) 95vw" width="740" height="494" src="/sites/default/files/styles/news_banner_370/public/2023-12/Nagy-portrait_larger-crop.jpg?h=afdc3185&amp;itok=0VqGp7HD" alt="&quot;&quot;"> </div> <span class="field field--name-uid field--type-entity-reference field--label-hidden"><span>Christopher.Sorensen</span></span> <span class="field field--name-created field--type-created field--label-hidden"><time datetime="2023-12-06T11:16:29-05:00" title="Wednesday, December 6, 2023 - 11:16" class="datetime">Wed, 12/06/2023 - 11:16</time> </span> <div class="clearfix text-formatted field field--name-field-cutline-long field--type-text-long field--label-above"> <div class="field__label">Cutline</div> <div class="field__item"><p><em>Andras Nagy, a senior investigator at Sinai Health’s&nbsp;Lunenfeld-Tanenbaum Research Institute (LTRI) and professor in U of T’s&nbsp;Temerty Faculty of Medicine, led research that created transplants in pre-clinical testing without the need for immune suppression</em></p> </div> </div> <div class="field field--name-field-author-reporters field--type-entity-reference field--label-hidden field__items"> <div class="field__item"><a href="/news/authors-reporters/jovana-drinjakovic" hreflang="en">Jovana Drinjakovic</a></div> </div> <div class="field field--name-field-topic field--type-entity-reference field--label-above"> <div class="field__label">Topic</div> <div class="field__item"><a href="/news/topics/breaking-research" hreflang="en">Breaking Research</a></div> </div> <div class="field field--name-field-story-tags field--type-entity-reference field--label-hidden field__items"> <div class="field__item"><a href="/news/tags/sinai-health" hreflang="en">Sinai Health</a></div> <div class="field__item"><a href="/news/tags/temerty-faculty-medicine" hreflang="en">Temerty Faculty of Medicine</a></div> <div class="field__item"><a href="/news/tags/lunenfeld-tanenbaum-research-institute" hreflang="en">Lunenfeld-Tanenbaum Research Institute</a></div> <div class="field__item"><a href="/news/tags/medicine-design" hreflang="en">Medicine by Design</a></div> <div class="field__item"><a href="/news/tags/research-innovation" hreflang="en">Research &amp; Innovation</a></div> </div> <div class="field field--name-field-subheadline field--type-string-long field--label-above"> <div class="field__label">Subheadline</div> <div class="field__item">The findings could lead to advancements in cell therapies for type 1 diabetes and heart failure</div> </div> <div class="clearfix text-formatted field field--name-body field--type-text-with-summary field--label-hidden field__item"><p>Researchers at&nbsp;Sinai Health&nbsp;and the&nbsp;Ƶ&nbsp;have developed a technology that may one day eliminate the need for immunosuppressive drugs in transplant patients.</p> <p>Through genetic modification of donor cells, the researchers successfully created transplants that persisted long-term in pre-clinical testing without the need for immune suppression.</p> <p>The findings raise hope that a similar strategy could be employed in human patients, potentially making transplantation safer and more widely available.</p> <p>“Our work paves the way for an ‘off-the-shelf’ supply of cells for therapies that could be safely given to many patients,” said&nbsp;<strong>Andras Nagy</strong>, a senior investigator at Sinai Health’s&nbsp;Lunenfeld-Tanenbaum Research Institute (LTRI) and professor in the department of obstetrics and gynaecology and the Institute of Medical Science at U of T’s&nbsp;Temerty Faculty of Medicine, who led the research.</p> <p>The study was&nbsp;<a href="https://www.nature.com/articles/s41551-023-01133-y">published in the journal&nbsp;<em>Nature Biomedical Engineering</em></a>.</p> <p>Immune rejection poses a major challenge in donor cell therapy, said Nagy, who is Canada Research Chair in Stem Cells and Regeneration and has done seminal work in the field. In such cases, the recipient’s immune system recognizes the transplanted cells as foreign invaders and launches an attack, leading to rejection.</p> <p>“Transplant and cell therapy patients are required to take immunosuppressive drugs&nbsp;– sometimes for the rest of their lives&nbsp;– to prevent their bodies from rejecting the transplant,” explained Nagy. The extended use of these drugs can lead to serious health issues, including recurring infections and an elevated cancer risk.</p> <p>Scientists worldwide have been exploring various solutions, including creating therapeutic cells from the patient’s own cells or encapsulating donor cells in inorganic material for protection.</p> <p>But these methods face challenges such as high costs, long preparation times and foreign body immune response, complicating their widespread and cost-effective application.</p> <p>Stem cells have the unique ability to divide indefinitely and give rise to specialized cells that form our organs. They make an ideal source for cell therapies as large numbers of cells can be obtained and converted into desired cell types to replace those lost to disease or injury.</p> <p>But there are major safety concerns: in addition to addressing immune-matching, scientists must ensure that no unwanted dividing cells remain in the transplant that could cause cancer in the future.</p> <p>Nagy, who established Canada’s first human embryonic stem cell line in 2005, has dedicated his career to engineering safeguards for future cell therapies. In 2018, his team <a href="https://www.sinaihealth.ca/news/new-discovery-a-built-in-killer-switch-eliminates-dividing-cells-from-lab-grown-transplant-tissue-to-improve-patient-safety/">published a landmark paper in&nbsp;<em>Nature</em></a>&nbsp;about&nbsp;a drug-inducible “kill-switch” called&nbsp;FailSafe&nbsp;that protects from cancer by eliminating unwanted proliferating cells in transplants.</p> <p>For the current study, postdoctoral researcher&nbsp;<strong>Jeff Harding</strong>&nbsp;and PhD student&nbsp;<strong>Kristina Vintersten-Nagy</strong>&nbsp;combined the kill-switch technology with a strategy they called “immune cloaking.”</p> <p>Nagy’s team selected eight key genes that regulate how the immune system responds to threats, including foreign cells. Forced overexpression of these genes in mouse embryonic stem cells prevented&nbsp;the immune system from recognizing them as foreign.</p> <p>The modification&nbsp;effectively created an immune cloak around the cells following their injection under the skin of genetically unmatched hosts.</p> <p>“Patient safety is paramount, and Dr. Andras Nagy is globally renowned for his sustained efforts to develop safeguards for future cell therapies,” said&nbsp;<strong>Anne-Claude Gingras</strong>, director of LTRI and vice-president of research at Sinai Health, and a professor of&nbsp;molecular genetics&nbsp;at Temerty Medicine.</p> <p>“This study demonstrates the combined potential of FailSafe and immune cloaking for the creation of a universal source of cells that could be applied to a multitude of diseases.”&nbsp;</p> <p>Uncloaked cells are typically rejected within 10 days of transplantation. In contrast, the cloaked cells persisted for more than nine months at the endpoint of the experiment. “This is the first time that we’ve been able to achieve this length of time without rejection in a fully functional immune system,” said Nagy, who is also a professor at Monash University in Australia.</p> <p>In another key finding, the researchers showed that unmodified cells can escape rejection when embedded into the tissue created by the cloaked donor cells below the skin surface. The protection extended to cells from another species, as shown by the ability of unmodified human cells to survive within a cloaked mouse graft.</p> <p>This suggests that modified cells also act as an immune-privileged implantation site for unmodified cells, with implications for interspecies transplants. Researchers&nbsp;at other institutions are exploring the potential of pigs as donors because their organs are very similar in size and function to humans.</p> <p>Building on this success, PhD student&nbsp;<strong>Huijuan Yang</strong>&nbsp;selected human counterparts of the eight immunomodulatory genes and used them to create the first FailSafe and cloaked human cells. Co-culturing these cells alongside human immune cells from an unmatched host revealed their ability to escape destruction, unlike their unmodified counterparts.</p> <p>This shows that cloaking has the potential to work for human patients as well, said Nagy.</p> <p>While the research is still at an early stage, it holds great promise for regenerative medicine and cell-based therapies. Nagy envisions injecting uncloaked insulin-producing cells, or islets, into subcutaneous cloaked tissue to treat diabetes. Subcutaneous cell delivery may be less risky for patients than the current approach, where islets are delivered into the liver and may interfere with its normal function, Nagy said.</p> <p>“This study gives invaluable insights into elegant alternatives to the toxic consequences of conventional immunosuppression,” said&nbsp;<strong>Michael Sefton</strong>, scientific director of&nbsp;<a href="https://mbd.utoronto.ca/">Medicine by Design</a>, a U of T&nbsp;<a href="https://isi.utoronto.ca/">institutional strategic initiative</a>&nbsp;focused on regenerative medicine that primarily funded the research, who is a <a href="https://www.provost.utoronto.ca/awards-funding/university-professors/">University Professor</a>&nbsp;in the department of chemical engineering and applied chemistry and the Institute of Biomedical Engineering in U of T’s Faculty of Applied Science &amp; Engineering.</p> <p>“These findings significantly advance cell therapies that can help people who live with chronic diseases such as type 1 diabetes or heart failure.”&nbsp;</p> <p>Beyond diabetes, Nagy is also developing applications for patients who have age-related macular degeneration, arthritis, chronic pain and lung diseases. To bring these advances to patients faster, he co-founded a startup company, panCELLa, which recently merged with the U.S. company Pluristyx to continue to develop safe and cost-effective clinical-grade, off-the-shelf&nbsp;cells for therapy.</p> <p>The research was funded by Medicine by Design, U of T, the Canadian Institutes for Health Research, Canada Research Chairs program and Ontario Research Fund.</p> <p>This story was&nbsp;<a href="https://www.sinaihealth.ca/news/scientists-create-cloaked-donor-cell-and-tissue-grafts-that-escape-rejection-by-the-immune-system/">originally published at <em>Sinai Health</em></a>.</p> </div> <div class="field field--name-field-news-home-page-banner field--type-boolean field--label-above"> <div class="field__label">News home page banner</div> <div class="field__item">Off</div> </div> Wed, 06 Dec 2023 16:16:29 +0000 Christopher.Sorensen 304768 at Working across disciplines, U of T and UHN researchers are rapidly revolutionizing lung transplant surgery /news/working-across-disciplines-u-t-and-uhn-researchers-are-rapidly-revolutionizing-lung-transplant <span class="field field--name-title field--type-string field--label-hidden">Working across disciplines, U of T and UHN researchers are rapidly revolutionizing lung transplant surgery</span> <div class="field field--name-field-featured-picture field--type-image field--label-hidden field__item"> <img loading="eager" srcset="/sites/default/files/styles/news_banner_370/public/GettyImages-1341427905-crop.jpg?h=afdc3185&amp;itok=AuFmpDBk 370w, /sites/default/files/styles/news_banner_740/public/GettyImages-1341427905-crop.jpg?h=afdc3185&amp;itok=EE2lX88P 740w, /sites/default/files/styles/news_banner_1110/public/GettyImages-1341427905-crop.jpg?h=afdc3185&amp;itok=vErznTEZ 1110w" sizes="(min-width:1200px) 1110px, (max-width: 1199px) 80vw, (max-width: 767px) 90vw, (max-width: 575px) 95vw" width="740" height="494" src="/sites/default/files/styles/news_banner_370/public/GettyImages-1341427905-crop.jpg?h=afdc3185&amp;itok=AuFmpDBk" alt="a pair of hands holds a paper cutout of a pair of lungs"> </div> <span class="field field--name-uid field--type-entity-reference field--label-hidden"><span>Christopher.Sorensen</span></span> <span class="field field--name-created field--type-created field--label-hidden"><time datetime="2022-11-29T09:28:25-05:00" title="Tuesday, November 29, 2022 - 09:28" class="datetime">Tue, 11/29/2022 - 09:28</time> </span> <div class="clearfix text-formatted field field--name-field-cutline-long field--type-text-long field--label-above"> <div class="field__label">Cutline</div> <div class="field__item">(Photo by Phira Phonruewiangphing via Getty Images)</div> </div> <div class="field field--name-field-author-reporters field--type-entity-reference field--label-hidden field__items"> <div class="field__item"><a href="/news/authors-reporters/tina-adamopoulos" hreflang="en">Tina Adamopoulos</a></div> </div> <div class="field field--name-field-topic field--type-entity-reference field--label-above"> <div class="field__label">Topic</div> <div class="field__item"><a href="/news/topics/our-community" hreflang="en">Our Community</a></div> </div> <div class="field field--name-field-story-tags field--type-entity-reference field--label-hidden field__items"> <div class="field__item"><a href="/news/tags/groundbreakers" hreflang="en">Groundbreakers</a></div> <div class="field__item"><a href="/news/tags/institutional-strategic-initiatives" hreflang="en">Institutional Strategic Initiatives</a></div> <div class="field__item"><a href="/news/tags/temerty-faculty-medicine" hreflang="en">Temerty Faculty of Medicine</a></div> <div class="field__item"><a href="/news/tags/artificial-intelligence" hreflang="en">Artificial Intelligence</a></div> <div class="field__item"><a href="/news/tags/graduate-students" hreflang="en">Graduate Students</a></div> <div class="field__item"><a href="/news/tags/medicine-design" hreflang="en">Medicine by Design</a></div> <div class="field__item"><a href="/news/tags/research-innovation" hreflang="en">Research &amp; Innovation</a></div> <div class="field__item"><a href="/news/tags/university-health-network" hreflang="en">University Health Network</a></div> </div> <div class="clearfix text-formatted field field--name-body field--type-text-with-summary field--label-hidden field__item"><p style="margin-bottom:11px">Hundreds of people in North America die each year waiting for a lung transplant – but it has little to do with a lack of donors.</p> <p style="margin-bottom:11px">About 80 per cent of donated lungs are deemed unsuitable for transplant, according to the International Society for Heart and Lung Transplantation. That’s because lungs are much more vulnerable to damage and deterioration than other organs.&nbsp;</p> <p style="margin-bottom:11px">But<b> Shaf Keshavjee</b> is working on a way to restore donated lungs – and help save lives.</p> <div class="image-with-caption left"> <p style="margin-bottom:11px"><img class="migrated-asset" src="/sites/default/files/Shaf-Keshavjee-crop.jpg" alt><em>Shaf Keshavjee</em></p> </div> <p style="margin-bottom:11px"><img class="migrated-asset" src="/sites/default/files/ShafKeshavjee_2.mp3" alt></p> <p style="margin-bottom:11px">He’s the architect of a system called<a href="/news/uhn-and-u-t-receive-24-million-federal-grant-transplant-research"> Ex Vivo Lung Perfusion (EVLP)</a> that preserves lungs outside the body in a transparent dome, so doctors can better prepare them for transplant. The system keeps donated lungs intact for up to 12 hours.</p> <p style="margin-bottom:11px">“We’ve taken everything we know about lung ventilation, how to look after an injured lung and the perfusion of [blood through] the lung together, to create a protective system outside of the body,” says Keshavjee, a surgeon-in-chief at the Sprott Department of Surgery at the University Health Network (UHN) and professor in the department of surgery at the Ƶ.</p> <p style="margin-bottom:11px">“People have tried to do this for almost 100 years.”</p> <p style="margin-bottom:11px">Keshavjee is continuing his work to refine the EVLP system as the lead investigator of the Organs by Design project. His research work is funded by U of T’s <a href="https://mbd.utoronto.ca/">Medicine by Design (MbD)</a> – a strategic initiative that brings together researchers at U of T and its affiliated hospitals at the convergence of science, engineering and medicine, to advance regenerative medicine discoveries and improve health outcomes. MbD is supported by Canada First Research Excellence Fund (CFREF). &nbsp;</p> <p style="margin-bottom:11px">To find solutions, each initiative draws on the breadth and depth of research at U of T, one of the world’s top public research universities, by bringing together flexible, multidisciplinary teams of researchers, students and partners from industry and government.&nbsp;</p> <p style="margin-bottom:11px">Increasing the number of healthy lungs for donation is one such challenge – and it’s far from the only lung transplant-related innovation that’s being advanced by U of T’s strategic initiatives.&nbsp;</p> <h4 style="margin-bottom: 11px;">Keeping lungs alive, outside of the body</h4> <p style="margin-bottom:11px">Stored in a glass dome that maintains temperature, humidity and sterilization, the EVLP system gently maintains the lung with a ventilator and filter system that ensures an adequate supply of oxygen, blood, nutrients and protein to the organ.&nbsp;</p> <p style="margin-bottom:11px">Prior to transplantation, the lung is reassessed for tissue elasticity, blood vessel pressure and oxygen capacity.&nbsp;</p> <p style="margin-bottom:11px">Keshavjee built the EVLP technology alongside <b>Marcelo Cypel</b>, a thoracic surgeon at UHN and professor of surgery at U of T. The researchers are building on a legacy of ground-breaking research in lung transplantation in Toronto that stretches back decades. That includes a team of surgeons at Toronto General Hospital (TGH), led by the hospital and U of T’s <strong>Joel Cooper</strong>, who<a href="https://www.uhn.ca/corporate/News/pages/event_lung_transplant_anniversary.aspx"> performed the first successful human lung transplant operation</a> in 1983.&nbsp;</p> <p style="margin-bottom:11px">In addition to restoring damaged lungs, the EVLP system provides surgeons with more information that can improve their ability to achieve a successful transplantation.</p> <p style="margin-bottom:11px">Keshavjee’s team is also working on a diagnostic tool that will allow surgeons to make rapid decisions based on crucial data collected by the EVLP system.&nbsp;</p> <h4 style="margin-bottom: 11px;">Retrieving life-saving data in minutes&nbsp;</h4> <p style="margin-bottom:11px"><b>Andrew Sage</b>, an assistant scientist at UHN’s Toronto General Hospital Research Institute and sessional lecturer at U of T, is building rapid diagnostics to swiftly supply doctors with a roadmap for lung repair.</p> <div class="image-with-caption right"> <p style="margin-bottom:11px"><img class="migrated-asset" src="/sites/default/files/Andrew-Sage_Headshot-crop.jpg" alt><em>Andrew Sage</em></p> </div> <p style="margin-bottom:11px">The map is needed because lung transplant operations are a race against time – and doctors need to make rapid decisions based on the best available information.</p> <p style="margin-bottom:11px">“When we put lungs on the EVLP platform, we are able to generate a tremendous amount of information on the ability of the lung to properly function and, importantly, this data represents lung function in isolation – free from confounding signals that arise from the rest of the body,” Sage says.&nbsp;</p> <p style="margin-bottom:11px">“Our goal is to develop novel testing modalities that can provide detailed information to the surgeon to make enhanced decisions about the organ.”</p> <p style="margin-bottom:11px">The rapid diagnostics tool – called the Toronto Lung Score – quickly details the injury status of the organ, inflammation and likelihood of ideal post-transplant outcomes, among other information, based on a small sample of solution that travels through the lungs on the EVLP system. It’s being developed in partnership with <a href="https://sqidiagnostics.com/">SQI Diagnostics</a>, a Toronto-based diagnostics development company.&nbsp;</p> <p style="margin-bottom:11px">At present, the tool provides results in under 40 minutes, but the team is working to trim the response time to less than 15.&nbsp;</p> <p style="margin-bottom:11px">The next step? <b>Bo Wang</b>, a professor at the <a href="https://tcairem.utoronto.ca/">Temerty Centre for Artificial Intelligence Research and Education in Medicine</a>, is working with the team to explore how AI and computer science can further improve analysis so practitioners can learn more from the ex vivo circuits.</p> <h4 style="margin-bottom: 11px;">A new gold standard to store transplant lungs</h4> <p style="margin-bottom:11px"><b>Ana Cristina Andreazza&nbsp;</b>is working on better ways to keep donor lungs healthy in the EVLP system – all of which promises to translate into better outcomes for patients.</p> <div class="image-with-caption left"> <p style="margin-bottom:11px"><img class="migrated-asset" src="/sites/default/files/Andreazza-Headshot-crop.jpg" alt><em>Ana Cristina Andreazza</em></p> </div> <p style="margin-bottom:11px">Andreazza,<b> </b>a professor in the departments of psychiatry and pharmacology and toxicology in the Temerty Faculty of Medicine, is leading efforts to improve storage of donated lungs through her research work with the <a href="https://www.mito2i.ca/">Mitochondrial Innovation Initiative</a> (MITO2i).</p> <p style="margin-bottom:11px">Andreazza heads an interdisciplinary team as scientific director of MITO2i. Made up of a network of clinicians, advocates and researchers across the university, NGOs and strategic partners, MITO2i is an ISI that discovers and supports new technologies and integrative platforms&nbsp;to understand the role mitochondria play in a wide range of diseases and how treating mitochondrial dysfunction can be therapeutic – and transform how clinicians approach the diagnosis and treatment of disease.</p> <p style="margin-bottom:11px">While the gold standard to store a transplanted lung is currently 4 C, Andreazza<b> </b>says the temperature puts the organ’s mitochondria – the powerhouses of cells – into a dormant state that could be impairing transplant outcomes.</p> <p style="margin-bottom:11px">“If we think through the lens of mitochondria metabolism, 4 C is not ideal,” says Andreazza, whose team is providing a better understanding of mitochondria’s role in human health and disease.</p> <p style="margin-bottom:11px">“When you transplant them from 4 C to a 37 C human body, you can imagine the clash that would happen.”</p> <p style="margin-bottom:11px">Working with Cypel, the surgeon at UHN, they found that increasing the temperature to 10 C better preserves mitochondria during EVLP, reducing the risk of rejection following transplant surgery.</p> <p style="margin-bottom:11px">A proof-of-concept pilot study, published last year in <a href="https://www.researchgate.net/publication/354615071_Static_lung_storage_at_10C_maintains_mitochondrial_health_and_preserves_donor_organ_function"><i>Science Translational Medicine</i></a><i>, </i>found that<i> </i>recipients of transplant lungs stored at 10 C&nbsp; required a ventilator for less than two days following surgery, on average. They demonstrated no signs of one of the earliest complications of a lung transplant, such as shortness of breath or dry cough, three days after the procedure.</p> <p style="margin-bottom:11px">A warmer storage temperature also prolongs the time donor lungs can be safely preserved, from the current maximum of six-to-eight hours, to between 10 and 16 hours. This, in turn, makes international organ transport possible, increasing availability for patients on waitlists.&nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp;&nbsp; &nbsp; &nbsp;</p> <p style="margin-bottom:11px">Looking ahead, researchers at MITO2i<u> </u>are seeking answers to three key questions. Are there better ways to monitor mitochondria? Can unhealthy organs be repaired? And how can mitochondria be improved before organ transplantation?</p> <h4 style="margin-bottom: 11px;">Mapping the genetic variation of mitochondria&nbsp;</h4> <p style="margin-bottom:11px">Enter<b> Erika Beroncal</b>, project manager at MITO2i and a master’s student in the department of pharmacology and toxicology in the Temerty Faculty of Medicine.</p> <div class="image-with-caption right"> <p style="margin-bottom:11px"><img alt src="/sites/default/files/Erika-Beroncal-headshot-crop.jpg" style="width: 250px; height: 250px;"><em>Erika Beroncal</em></p> </div> <p style="margin-bottom:11px">One of 13 recipients of MITO2i’s<a href="https://www.mito2i.ca/awardees"> 2022 Graduate Student Scholarship Awards</a>, Beroncal is embarking on a research project to examine the genetic variance of mitochondria and its importance in lung transplant success.&nbsp;</p> <p style="margin-bottom:11px">She recently presented the project at the second annual<a href="https://www.mito2i.ca/2022-research-symposium"> MITO2i Research Symposium</a>, a two-day virtual event that brought faculty, students and research partners together to share new developments in mitochondrial research and medicine.&nbsp;</p> <p style="margin-bottom:11px">Ultimately, Beroncal hopes to contribute to knowledge that will open doors for novel therapeutic interventions to enhance lung transplant outcomes.</p> <p style="margin-bottom:11px">“By working with people across disciplines to produce knowledge about mitochondria, I’m seeing current developments and learning how it affects real life,” Beroncal says.</p> <p style="margin-bottom:11px">“Through my research work, I know I’m able to make an impact in this field.”</p> <p style="margin-bottom:11px"><em>This article <a href="/news/tags/groundbreakers">is&nbsp;part of a multimedia series</a>&nbsp;about U of T's Institutional Strategic Initiatives program – which seeks to make life-changing advancements in everything from infectious diseases to social justice –&nbsp;and the research community that's driving it.</em></p> <p style="margin-bottom:11px">&nbsp;</p> </div> <div class="field field--name-field-news-home-page-banner field--type-boolean field--label-above"> <div class="field__label">News home page banner</div> <div class="field__item">Off</div> </div> Tue, 29 Nov 2022 14:28:25 +0000 Christopher.Sorensen 178364 at Students push the boundaries of research and innovation: Groundbreakers S2 Ep.4 /news/students-push-boundaries-research-and-innovation-groundbreakers-s2-ep4 <span class="field field--name-title field--type-string field--label-hidden">Students push the boundaries of research and innovation: Groundbreakers S2 Ep.4</span> <span class="field field--name-uid field--type-entity-reference field--label-hidden"><span>Christopher.Sorensen</span></span> <span class="field field--name-created field--type-created field--label-hidden"><time datetime="2022-11-08T10:04:32-05:00" title="Tuesday, November 8, 2022 - 10:04" class="datetime">Tue, 11/08/2022 - 10:04</time> </span> <div class="field field--name-field-youtube field--type-youtube field--label-hidden field__item"><figure class="youtube-container"> <iframe src="https://www.youtube.com/embed/AnvrorYh_pY?wmode=opaque" width="450" height="315" id="youtube-field-player" class="youtube-field-player" title="Embedded video for Students push the boundaries of research and innovation: Groundbreakers S2 Ep.4" aria-label="Embedded video for Students push the boundaries of research and innovation: Groundbreakers S2 Ep.4: https://www.youtube.com/embed/AnvrorYh_pY?wmode=opaque" frameborder="0" allowfullscreen></iframe> </figure> </div> <div class="field field--name-field-topic field--type-entity-reference field--label-above"> <div class="field__label">Topic</div> <div class="field__item"><a href="/news/topics/our-community" hreflang="en">Our Community</a></div> </div> <div class="field field--name-field-story-tags field--type-entity-reference field--label-hidden field__items"> <div class="field__item"><a href="/news/tags/groundbreakers" hreflang="en">Groundbreakers</a></div> <div class="field__item"><a href="/news/tags/institutional-strategic-initiatives" hreflang="en">Institutional Strategic Initiatives</a></div> <div class="field__item"><a href="/news/tags/temerty-faculty-medicine" hreflang="en">Temerty Faculty of Medicine</a></div> <div class="field__item"><a href="/news/tags/alumni" hreflang="en">Alumni</a></div> <div class="field__item"><a href="/news/tags/graduate-students" hreflang="en">Graduate Students</a></div> <div class="field__item"><a href="/news/tags/medicine-design" hreflang="en">Medicine by Design</a></div> <div class="field__item"><a href="/news/tags/research-innovation" hreflang="en">Research &amp; Innovation</a></div> <div class="field__item"><a href="/news/tags/robotics" hreflang="en">Robotics</a></div> <div class="field__item"><a href="/news/tags/u-t-mississauga" hreflang="en">U of T Mississauga</a></div> </div> <div class="clearfix text-formatted field field--name-body field--type-text-with-summary field--label-hidden field__item"><p class="xx"><span style="background:white"><span style="border:1pt none windowtext; padding:0cm">From launching rovers into space to exploring whether green cannabinoids can treat epilepsy in children, students&nbsp;at the Ƶ are taking research and innovation in bold new directions.</span></span></p> <p class="xx"><span style="background:white"><span style="border:1pt none windowtext; padding:0cm">In Ep. 4 of the&nbsp;<i>Groundbreakers</i>&nbsp;video series,&nbsp;</span><span style="border:1pt none windowtext; padding:0cm">host&nbsp;<b>Ainka&nbsp;Jess</b></span><b>&nbsp;</b><span style="border:1pt none windowtext; padding:0cm">goes behind the scenes with student researchers from&nbsp;</span><span style="border:1pt none windowtext; padding:0cm">the&nbsp;</span><a href="https://robotics.utoronto.ca/" target="_blank"><span style="border:1pt none windowtext; padding:0cm">Robotics Institute</span></a><span style="border:1pt none windowtext; padding:0cm">&nbsp;and&nbsp;</span><a href="https://mbd.utoronto.ca/" target="_blank"><span style="border:1pt none windowtext; padding:0cm">Medicine by Design</span></a><span style="border:1pt none windowtext; padding:0cm">&nbsp;strategic initiatives, as well as the&nbsp;</span><a href="https://entrepreneurs.utoronto.ca/for-entrepreneurs/black-founders-network/" target="_blank"><span style="border:1pt none windowtext; padding:0cm">Black Founders Network</span></a><span style="border:1pt none windowtext; padding:0cm">.</span></span></p> <p class="xx"><span style="background:white"><span style="border:1pt none windowtext; padding:0cm">Some of their work is literally out of this world.</span></span></p> <p class="x"><span style="background:white">“I think as humans we are very curious creatures and I see planetary robots as a way to extend our reach in the solar system, so I’m actually really excited about what these rovers can do in the future,” says <b>Olivier Lamarre</b>, a PhD candidate in planetary robotics at U of T’s&nbsp;<a href="https://starslab.ca/" target="_blank"><span style="border:1pt none windowtext; padding:0cm">STARS Laboratory</span></a>.</span></p> <p class="x"><span style="background:white"><span style="border:1pt none windowtext; padding:0cm">The episode also features&nbsp;<b>Kareem Abdur-Rashid</b> and<b>&nbsp;Kamaluddin Abdur-Rashid</b> – both alumni of U of T and co-founders and <a href="https://www.chemistry.utoronto.ca/news/father-and-son-team-create-green-cannabinoids">co-directors of Kare Chemical Technologies</a> – and<b>&nbsp;Justine&nbsp;Bajohr</b>,&nbsp;a PhD candidate <a href="https://www.faiz-lab.com/">in the lab of <b>Maryam Faiz</b></a>, an assistant professor in the department of surgery in the Temerty Faculty of Medicine.</span></span></p> <p class="xx"><span style="background:white"><i><span style="border:1pt none windowtext; padding:0cm">Groundbreakers</span></i><span style="border:1pt none windowtext; padding:0cm">&nbsp;is a multimedia series that includes articles at <i>U of T News</i> and features research leaders involved with U of T’s <a href="https://isi.utoronto.ca/">Institutional Strategic Initiatives</a>, whose work will transform lives.</span></span></p> <h3 class="xx"><a href="https://www.youtube.com/watch?v=AnvrorYh_pY"><span style="background:white"><span style="border:1pt none windowtext; padding:0cm">Watch S2 Ep.4 of Groundbreakers</span></span></a></h3> <p>&nbsp;</p> <p>&nbsp;</p> </div> <div class="field field--name-field-news-home-page-banner field--type-boolean field--label-above"> <div class="field__label">News home page banner</div> <div class="field__item">Off</div> </div> Tue, 08 Nov 2022 15:04:32 +0000 Christopher.Sorensen 178033 at Researchers shrink brain tumours with gold nanoparticles, develop ‘mini brains’ to study psychiatric disorders /news/researchers-shrink-brain-tumours-gold-nanoparticles-develop-mini-brains-study-psychiatric <span class="field field--name-title field--type-string field--label-hidden">Researchers shrink brain tumours with gold nanoparticles, develop ‘mini brains’ to study psychiatric disorders</span> <div class="field field--name-field-featured-picture field--type-image field--label-hidden field__item"> <img loading="eager" srcset="/sites/default/files/styles/news_banner_370/public/GettyImages-1075411486-crop_0.jpg?h=afdc3185&amp;itok=C-ftVNHK 370w, /sites/default/files/styles/news_banner_740/public/GettyImages-1075411486-crop_0.jpg?h=afdc3185&amp;itok=9NrGZeuQ 740w, /sites/default/files/styles/news_banner_1110/public/GettyImages-1075411486-crop_0.jpg?h=afdc3185&amp;itok=jyGN_-Jm 1110w" sizes="(min-width:1200px) 1110px, (max-width: 1199px) 80vw, (max-width: 767px) 90vw, (max-width: 575px) 95vw" width="740" height="494" src="/sites/default/files/styles/news_banner_370/public/GettyImages-1075411486-crop_0.jpg?h=afdc3185&amp;itok=C-ftVNHK" alt="a technician helps a woman into an MRI machine"> </div> <span class="field field--name-uid field--type-entity-reference field--label-hidden"><span>Christopher.Sorensen</span></span> <span class="field field--name-created field--type-created field--label-hidden"><time datetime="2022-10-18T10:03:07-04:00" title="Tuesday, October 18, 2022 - 10:03" class="datetime">Tue, 10/18/2022 - 10:03</time> </span> <div class="clearfix text-formatted field field--name-field-cutline-long field--type-text-long field--label-above"> <div class="field__label">Cutline</div> <div class="field__item">(Photo by Aja Koska/Getty Images)</div> </div> <div class="field field--name-field-author-reporters field--type-entity-reference field--label-hidden field__items"> <div class="field__item"><a href="/news/authors-reporters/tina-adamopoulos" hreflang="en">Tina Adamopoulos</a></div> </div> <div class="field field--name-field-topic field--type-entity-reference field--label-above"> <div class="field__label">Topic</div> <div class="field__item"><a href="/news/topics/our-community" hreflang="en">Our Community</a></div> </div> <div class="field field--name-field-story-tags field--type-entity-reference field--label-hidden field__items"> <div class="field__item"><a href="/news/tags/groundbreakers" hreflang="en">Groundbreakers</a></div> <div class="field__item"><a href="/news/tags/institutional-strategic-initiatives" hreflang="en">Institutional Strategic Initiatives</a></div> <div class="field__item"><a href="/news/tags/prime" hreflang="en">PRiME</a></div> <div class="field__item"><a href="/news/tags/temerty-faculty-medicine" hreflang="en">Temerty Faculty of Medicine</a></div> <div class="field__item"><a href="/news/tags/donnelly-centre-cellular-biomolecular-research" hreflang="en">Donnelly Centre for Cellular &amp; Biomolecular Research</a></div> <div class="field__item"><a href="/news/tags/chemistry" hreflang="en">Chemistry</a></div> <div class="field__item"><a href="/news/tags/faculty-arts-science" hreflang="en">Faculty of Arts &amp; Science</a></div> <div class="field__item"><a href="/news/tags/graduate-students" hreflang="en">Graduate Students</a></div> <div class="field__item"><a href="/news/tags/leslie-dan-faculty-pharmacy" hreflang="en">Leslie Dan Faculty of Pharmacy</a></div> <div class="field__item"><a href="/news/tags/medicine-design" hreflang="en">Medicine by Design</a></div> </div> <div class="clearfix text-formatted field field--name-body field--type-text-with-summary field--label-hidden field__item"><p style="margin-bottom:11px">Researchers at the Ƶ are inching closer to realizing a life-saving brain cancer treatment by using gold nanoparticles to make radiation therapy more effective and less toxic for patients.&nbsp;</p> <p style="margin-bottom:11px">In their battle against glioblastoma multiforme (GBM), a rare, fast-growing cancer that begins in the brain, the multidisciplinary team has discovered that the nanoparticles can keep radiation tightly focused on the tumour, shrinking its size and preventing damage elsewhere in the body.</p> <p style="margin-bottom:11px">Only a handful of researchers around the world are focused on radiolabeled nanoparticle&nbsp;research for brain tumours.</p> <div class="image-with-caption left"> <p style="margin-bottom:11px"><img class="migrated-asset" src="/sites/default/files/Raymond-Reilly-square_0.jpg" alt><em>Raymond Reilly</em></p> </div> <p style="margin-bottom:11px">“There is a small group of scientists working on radiation nanomedicines globally – and an even smaller group studying the therapeutic use of radiolabeled gold nanoparticles,” says <b>Raymond Reilly,</b> a renowned specialist in radiopharmaceuticals and professor in the Leslie Dan Faculty of Pharmacy who is supervising the team.</p> <p style="margin-bottom:11px">“To my knowledge, we're one of the few groups in the world that have studied local infusion of radiolabeled gold nanoparticles for treatment of brain tumours.”</p> <p style="margin-bottom:11px"><img class="migrated-asset" src="/sites/default/files/RaymondReilly_2.mp3" alt></p> <p>&nbsp;</p> <h4 style="margin-bottom: 11px;">Anchoring radioisotopes in the brain&nbsp;</h4> <p style="margin-bottom:11px">In animal studies, the use of gold nanoparticles in radiation resulted in tumours that were no longer detectable by MRI four weeks after the treatment. The researchers also found evidence of prolonged survival – and a potential cure – following the 150-day trial.&nbsp;</p> <div class="image-with-caption right"> <p style="margin-bottom:11px"><img class="migrated-asset" src="/sites/default/files/Constantine-Georgiou-square.jpg" alt><em>Constantine Georgiou</em></p> </div> <p style="margin-bottom:11px">“We use gold nanoparticles to hold the radiation, or radioisotope, where we inject it into the brain,” says <b>Constantine Georgiou</b>,<b> </b>a graduate student in the department of pharmaceutical studies who works with Reilly.&nbsp;</p> <p style="margin-bottom:11px">“Without the gold nanoparticle, the radiation leaves the brain tumour, making it non-effective.”&nbsp;</p> <p style="margin-bottom:11px">The radiation also effectively erased tumour cells without causing any apparent damage to the brain or other tissues in the body – travelling no more than two millimetres from the site of injection. In other words, there appears to be no toxicity associated with the treatment.&nbsp;</p> <p style="margin-bottom:11px">To evaluate the effectiveness of the therapy, Georgiou used innovative imaging techniques such as single-photon emission computed tomography (SPECT) imaging, a type of nuclear medicine imaging that allows researchers to visualize where the gold nanoparticles are located in the brain, and bioluminescence and MRI imaging to track the growth of the tumour.&nbsp;</p> <p style="margin-bottom:11px">The project was first developed under <b>Noor Al-saden</b>, one of 10 trainees at U of T&nbsp;who took part in the inaugural 2019 <a href="https://www.prime.utoronto.ca/prime-fellowship-details">PRiME Fellowship Awards</a> – a program to propel high-risk, high-reward, multidisciplinary research in precision medicine.&nbsp;<a href="https://www.prime.utoronto.ca/">PRiME</a> is an <a href="https://isi.utoronto.ca/#:~:text=The%20Institutional%20Strategic%20Initiatives%20portfolio,industry%2C%20community%20and%20philanthropic%20partners.">Institutional Strategic Initiative</a> (ISI) at U of T that connects scientists, engineers and other innovators across different disciplines to accelerate drug discovery, diagnostics and understanding of disease biology.</p> <p style="margin-bottom:11px">Preliminary results from Al-saden’s PRiME research and a seed grant from the Brain Tumour Foundation of Canada helped Reilly’s group secure a $200,000 Canadian Cancer Society Innovation Grant.&nbsp;</p> <p style="margin-bottom:11px">The development of radiation nanomedicine requires a multidisciplinary approach.&nbsp;</p> <p style="margin-bottom:11px">At U of T, the research would not have been possible without the expertise of world-renowned polymer chemist <b>Mitch Winnik</b>, a professor in the department of chemistry in Faculty of Arts &amp; Science. That’s because the radioisotope – in this case, Lutetium-177 – is attached to gold nanoparticles by a polymer synthesised by Winnik’s group, a substance made of large molecules with various metal-binding sites.&nbsp;</p> <p style="margin-bottom:11px">The team’s next research phase will take place in a new space at U of T: the Good Manufacturing Practices (GMP) facility in the Leslie Dan Faculty of Pharmacy. Made possible by a $1.3 million grant awarded to Reilly from the Canadian Foundation for Innovation and Ontario Research Fund, the facility was launched earlier this year to create radiopharmaceuticals for clinical trials.&nbsp;</p> <p style="margin-bottom:11px">Georgiou and Reilly are currently studying radiation nanomedicine combined with immunotherapy to provide a more durable tumour response to treat GBM. The group also plans to study the effectiveness of other radioisotopes attached to the gold nanoparticles, which may achieve even more precision in erasing cancer cells.&nbsp;</p> <h4 style="margin-bottom: 11px;">A deeper understanding of energy metabolism in brain disorders by making ‘mini brains’</h4> <p style="margin-bottom:11px">Reilly and Georgiou’s research isn’t the only innovative, brain-focused project that’s being supported by PRiME.</p> <div class="image-with-caption left"> <p style="margin-bottom:11px"><img class="migrated-asset" src="/sites/default/files/angeladuong-square_0.jpg" alt><em>Angela Duong</em></p> </div> <p style="margin-bottom:11px">Research by<b> Angela Duong</b>, a U of T alumna and a 2019 PRiME fellow, developed 2D and 3D brain models from patients to gain insights into the role that mitochondrial function plays in neuronal activity – specifically in patients with bipolar disorder.&nbsp;</p> <p style="margin-bottom:11px">Working alongside <b>Ana Cristina Andreazza</b> – a professor in the departments of pharmacology and toxicology and psychiatry in the Temerty Faculty of Medicine, with a cross appointment at the Centre for Addiction and Mental Health – Duong built 3D <i>in vitro </i>cultures of brain cells, also known as cerebral organoids, to identify biological targets that can be used to guide the development of therapeutics. In doing so, Duong overcame longstanding hurdles in understanding the biology of patients with psychiatric disorders since researchers previously relied on two limited avenues for investigation: post-mortem brain samples, which are scarce, and brain imaging technologies which are expensive and may require radioactive exposure.</p> <p style="margin-bottom:11px">Duong describes her cerebral organoids as “mini brains” that retain patient genetic background, allowing researchers to study human-specific processes that might be related to the clinical diagnosis of the patients.&nbsp; She says this tool is useful for disease modelling compared to brain samples from animals which do not carry the complex human genes that cause psychiatric disorders.</p> <p style="margin-bottom:11px">“In the brain, 20 per cent of our body’s total energy budget is used to support neurotransmission. This is a very energy-demanding process that allows brain cells to communicate with each other, Duong says. “So, if there is metabolic dysfunction in the brain, the process of neurotransmission is also affected, which we think is related to the symptoms and mood changes that we commonly see in patients with psychiatric disorders.”</p> <p style="margin-bottom:11px">“By developing 'mini brains' to function as disease models, we can learn what metabolic changes are going on in the brain of actual patients with brain diseases without invasive brain biopsies or studying the brains of mice or rats."</p> <p style="margin-bottom:11px">To do this, Duong collected blood samples from patients with and without bipolar disorder and isolated their white blood cells. The cells were then reprogrammed into induced pluripotent stem cells (iPSCs), a stem cell that can be generated directly from a somatic cell, any cell of a living organism other than reproductive ones. Using these iPSCs, Duong later created 2D and 3D brain cells, or organoids.</p> <p style="margin-bottom:11px">Duong’s project was among the first to fully characterize the brain’s mitochondrial health, from white blood cells to iPSCs to cerebral organoids. That, in turn, offered validation about whether mitochondria stay healthy throughout the reprogramming and differentiation process. This study provides important groundwork for creating more sophisticated patient 2D and 3D brain cells for disease modelling and the study of mitochondrial dysfunction across a wide range of brain diseases.</p> <p style="margin-bottom:11px">The achievement required the multidisciplinary collaboration of three different U of T labs.&nbsp;</p> <div class="image-with-caption right"> <p style="margin-bottom:11px"><img class="migrated-asset" src="/sites/default/files/Liliana-Attisano-photo-2-square_0.jpg" alt><em>Liliana Attisano</em></p> </div> <p style="margin-bottom:11px">In addition to Andreazza’s lab, the PRiME project brought in expertise from two professors at the Temerty Faculty of Medicine to work on the 3D engineered organoids: <b>Liliana Attisano</b>, a professor of biochemistry in the Temerty Faculty of Medicine and at the Donnelly Centre for Cellular and Biomolecular Research, and <b>Martin Beaulieu</b>, an associate professor in the department of pharmacology and toxicology in the Temerty Faculty of Medicine.&nbsp;</p> <h4 style="margin-bottom: 11px;">Building self-developing brain cells</h4> <p style="margin-bottom:11px">Organoid production relies on the cell’s self-organizing properties to develop required cell types.</p> <p style="margin-bottom:11px">The goal of Attisano’s lab was to develop protocols to produce cerebral organoids that were all the same size and shape to decrease variability, making it easier for researchers to find the answers to their questions. To accomplish this, researchers added growth factors or inhibitors that moved the cells into a neural lineage. After that, the cells divided and developed for about a month – just as they would in a human brain. The lineage can also be modified to make organoids for other body parts, such as the liver.</p> <p style="margin-bottom:11px">Beaulieu’s lab, meanwhile, provided equipment and resources to characterize the electroactivity of the neurons within the organoids.</p> <p style="margin-bottom:11px">Duong’s technological model is now being used by Andreazza to further develop cerebral organoids to further investigate a range of psychiatric conditions.</p> <p style="margin-bottom:11px">Meanwhile, Attisano is making cerebral organoids available for researchers across Toronto with an organoid<a href="https://braincanada.ca/news/latest-platform-support-grant-to-make-advanced-brain-models-accessible-to-canadas-neuroscience-research-community/"> production platform called Applied Organoid Core (ApOC)</a>, funded by the Brain Canada Foundation’s 2019 Platform Support Grant, and U of T’s <a href="https://mbd.utoronto.ca/">Medicine by Design</a> strategic initiative. The ApOC is a $1,425,000 grant. Through this project, Attisano is collaborating with other researchers who want to use cerebral organoids to map human brain development and disorders such as epilepsy.</p> <p style="margin-bottom:11px">“When it comes down to it, brain disorders are simply a kind of alteration in molecular components that result in altered behaviour. It’s no different from a mutation that makes you susceptible to cancer. But we never had the capacity to study this,” Attisano says.&nbsp;</p> <p style="margin-bottom:11px">“Cerebral organoids give us that potential.”&nbsp;</p> <p style="margin-bottom:11px"><em>This article <a href="/news/tags/groundbreakers">is&nbsp;part of a multimedia series</a>&nbsp;about U of T's Institutional Strategic Initiatives program – which seeks to make life-changing advancements in everything from infectious diseases to social justice –&nbsp;and the research community that's driving it.</em></p> <p style="margin-bottom:11px">&nbsp;</p> <p style="margin-bottom:11px">&nbsp;</p> <p style="margin-bottom:11px">&nbsp;</p> <p style="margin-bottom:11px">&nbsp;</p> <p style="margin-bottom:11px">&nbsp;</p> </div> <div class="field field--name-field-news-home-page-banner field--type-boolean field--label-above"> <div class="field__label">News home page banner</div> <div class="field__item">Off</div> </div> Tue, 18 Oct 2022 14:03:07 +0000 Christopher.Sorensen 177570 at Experts explore strategies for strengthening Canada’s bioinnovation ecosystem at Medicine by Design event /news/experts-explore-strategies-strengthening-canada-s-bioinnovation-ecosystem-medicine-design-event <span class="field field--name-title field--type-string field--label-hidden">Experts explore strategies for strengthening Canada’s bioinnovation ecosystem at Medicine by Design event</span> <div class="field field--name-field-featured-picture field--type-image field--label-hidden field__item"> <img loading="eager" srcset="/sites/default/files/styles/news_banner_370/public/2023-04/UofT6688_20141111_CollegeandUniversity_8520.jpeg?h=afdc3185&amp;itok=XS_WFyNT 370w, /sites/default/files/styles/news_banner_740/public/2023-04/UofT6688_20141111_CollegeandUniversity_8520.jpeg?h=afdc3185&amp;itok=XASgyGYY 740w, /sites/default/files/styles/news_banner_1110/public/2023-04/UofT6688_20141111_CollegeandUniversity_8520.jpeg?h=afdc3185&amp;itok=OQYvT1oZ 1110w" sizes="(min-width:1200px) 1110px, (max-width: 1199px) 80vw, (max-width: 767px) 90vw, (max-width: 575px) 95vw" width="740" height="494" src="/sites/default/files/styles/news_banner_370/public/2023-04/UofT6688_20141111_CollegeandUniversity_8520.jpeg?h=afdc3185&amp;itok=XS_WFyNT" alt="College and University"> </div> <span class="field field--name-uid field--type-entity-reference field--label-hidden"><span>Christopher.Sorensen</span></span> <span class="field field--name-created field--type-created field--label-hidden"><time datetime="2022-01-05T12:06:42-05:00" title="Wednesday, January 5, 2022 - 12:06" class="datetime">Wed, 01/05/2022 - 12:06</time> </span> <div class="clearfix text-formatted field field--name-field-cutline-long field--type-text-long field--label-above"> <div class="field__label">Cutline</div> <div class="field__item"><p>Toronto’s MaRS Discovery District, which shares close connections to U of T and its hospital partners, is a major Canadian hub for biotechnology innovation in Canada (photo by Makeda Marc-Ali)</p> </div> </div> <div class="field field--name-field-author-reporters field--type-entity-reference field--label-hidden field__items"> <div class="field__item"><a href="/news/authors-reporters/julie-crljen" hreflang="en">Julie Crljen</a></div> </div> <div class="field field--name-field-topic field--type-entity-reference field--label-above"> <div class="field__label">Topic</div> <div class="field__item"><a href="/news/topics/our-community" hreflang="en">Our Community</a></div> </div> <div class="field field--name-field-story-tags field--type-entity-reference field--label-hidden field__items"> <div class="field__item"><a href="/news/tags/temerty-faculty-medicine" hreflang="en">Temerty Faculty of Medicine</a></div> <div class="field__item"><a href="/news/tags/donnelly-centre-cellular-biomolecular-research" hreflang="en">Donnelly Centre for Cellular &amp; Biomolecular Research</a></div> <div class="field__item"><a href="/news/tags/institute-health-policy-management-and-evaluation" hreflang="en">Institute of Health Policy Management and Evaluation</a></div> <div class="field__item"><a href="/news/tags/munk-school-global-affairs-public-policy-0" hreflang="en">Munk School of Global Affairs &amp; Public Policy</a></div> <div class="field__item"><a href="/news/tags/ccrm" hreflang="en">CCRM</a></div> <div class="field__item"><a href="/news/tags/dalla-lana-school-public-health" hreflang="en">Dalla Lana School of Public Health</a></div> <div class="field__item"><a href="/news/tags/faculty-applied-science-engineering" hreflang="en">Faculty of Applied Science &amp; Engineering</a></div> <div class="field__item"><a href="/news/tags/faculty-arts-science" hreflang="en">Faculty of Arts &amp; Science</a></div> <div class="field__item"><a href="/news/tags/medicine-design" hreflang="en">Medicine by Design</a></div> <div class="field__item"><a href="/news/tags/university-health-network" hreflang="en">University Health Network</a></div> </div> <div class="clearfix text-formatted field field--name-body field--type-text-with-summary field--label-hidden field__item"><p>What can the unprecedented speed of vaccine development during the COVID-19 pandemic teach us about strengthening our bioinnovation ecosystem?</p> <p>For David Walt, a professor at the Wyss Institute for Biologically Inspired Engineering at Harvard University, many of the pandemic’s innovations promise to have a lasting effect&nbsp;since, as a society, we “now have some of the tools in place to help catalyze continued innovation and collaboration” in the field.</p> <p>“Everyone who was working on [COVID-19] had the potential to be affected by it. It was a global imperative that we all co-operate,” he said during a recent symposium hosted by the Ƶ’s Medicine by Design program.</p> <p>Walt, who&nbsp;co-leads the&nbsp;Mass General Brigham Center for COVID Innovation, made the remarks&nbsp;during a panel discussion titled&nbsp;“Strengthening Our Bioinnovation Ecosystem” that followed his plenary talk.</p> <div> <div class="image-with-caption left"><img alt src="/sites/default/files/2023-04/David-Walt-crop.jpeg" style="width: 200px; height: 300px;"><em><span style="font-size:12px;">David R. Walt</span></em></div> </div> <p>The symposium – “A Systems Approach to Regenerative Medicine” – was held over two days and&nbsp;attracted more than 500 registrants.&nbsp;It included talks from invited speakers&nbsp;Ruslan Medzhitov, a professor in the Yale School of Medicine at Yale University,&nbsp;on the topic of&nbsp;inflammation systems&nbsp;biology;&nbsp;and&nbsp;Linda G. Griffith, a professor in the department of biological and medicalengineering at the Massachusetts Institute of Technology (MIT),&nbsp;who spoke about organ-on-chip technologies, including&nbsp;their&nbsp;application&nbsp;to endometriosis.</p> <p>The panel discussion on strengthening the bioinnovation ecosystem looked at the symposium’s broad theme in a more “holistic fashion,” said Medicine by Design Executive Director&nbsp;<strong>Michael Sefton</strong>, who&nbsp;is also a&nbsp;<a href="https://www.provost.utoronto.ca/awards-funding/university-professors/">University Professor</a>&nbsp;in the department of chemical engineering and applied chemistry and the Institute of Biomedical Engineering.</p> <p>“[We’re] looking at health-care systems and innovation systems with a focus on health policy and social science lessons learned from COVID-19.”&nbsp;</p> <p>The panel discussion was timely as Medicine by Design seeks to ensure the bioinnovation system in Canada is well-prepared to advance the regenerative discoveries coming out of the labs of researchers at U of T and its partner hospitals.</p> <p>“We are looking forward to continuing to excel and to prepare the future of human health – to continue to transform but also translate,” said Sefton, whose lab is located at the Donnelly Centre for Cellular &amp; Bimolecular Research, in his opening remarks. “Our goal is to not just write great papers but to also show that these papers can be translated into impact –maybe not immediately, but certainly over the next five or ten years, if not beyond.”</p> <p>The impact of COVID-19 on the bioinnovation pipeline was just one of themes panelists touched on during a wide-ranging discussion. The panel was moderated by&nbsp;<strong>Shiri Breznitz</strong>, who is an associate professor at the Munk School of Global Affairs &amp; Public Policy and the director of the master of global affairs program at U of T.</p> <h4>A clinical pull rather than technology push</h4> <p>Often innovations begin with an engineer or scientist inventing a technology and filing a patent before determining the clinical need for their product. But using “design thinking” to innovate can accelerate the timeline of implementation by years, Walt said during his talk.</p> <p>“If you start with the clinical need first rather than the technology – a clinical pull rather than a technology push – then you come up with a [design-thinking] model.”</p> <p>In the design-thinking model, clinicians identify unmet needs&nbsp;and then scientists and engineers develop solutions to solve those problems. Design thinking “starts with the problem. It has a human-centred core,” said Walt.</p> <h4>Collaboration and trust are important elements of an ecosystem</h4> <div> <div class="image-with0caption right"> <div class="image-with-caption right"><img alt src="/sites/default/files/2023-04/Catherine%20Beaudry_2.jpeg" style="width: 200px; height: 237px;"><em><span style="font-size:12px;">Catherine Beaudry</span></em></div> </div> </div> <p>The strength of an ecosystem can be measured by its level of collaboration and trust, said panelist&nbsp;Catherine Beaudry, who leads the&nbsp;Partnership for the Organization of Innovation and New Technologies (4POINTO)&nbsp;and is a professor at Polytechnique Montréal.</p> <p>“At the heart of all these models, you have to remember that it’s individuals who are collaborating with other individuals. The glue that maintains the ecosystem is trust.”</p> <p>Beaudry pointed to the importance of having strong intellectual property policies and making sure innovators are collaborating with regulators early in the therapeutics or technology development process as important elements of building trust. She added that using more thoughtful metrics – key performance indicators, or KPIs – is also a key part of measuring the health of an ecosystem.</p> <p>“Bean counting is not the way to go. We need to measure how organizations collaborate, whether these relationships last over time, and what comes out of them.”</p> <h4>Aligning towards a common goal</h4> <div class="image-with-caption left"> <div><img alt src="/sites/default/files/2023-04/Beate_Sander_Photo%20540x540.jpg.jpg" style="width: 200px; height: 237px;"><em><span style="font-size:12px;">Beate Sander</span></em></div> </div> <p><strong>Beate Sander</strong>, a scientist and the director of&nbsp;population health economics research for the <a href="https://theta.utoronto.ca/">Toronto Health Economics and Technology Assessment Collaborative (THETA)</a>, pointed to how the speed of vaccine development during the pandemic showed us how the seemingly impossible could be possible.</p> <p>“The pandemic has shown that we cannot separate health and the economy,” said Sander, who is also an associate professor at the Institute of Health Policy, Management and Evaluation at the Dalla Lana School of Public Health.</p> <p>&nbsp;“[In the pandemic] everyone is rallying around similar goals. So everything aligned in a time of very high pressure, very high uncertainty. How do we move what we have now to post-pandemic times when all that pressure is gone, and everyone will be inclined to go back to what we’ve done previously?”</p> <p>Sander is an expert in health technology assessment, a multi-disciplinary process that looks at the value of a technology from a wide range of perspectives – not just technical properties, but also many other factors including economic considerations, social and legal impacts and patient perspectives.</p> <p>Where normally innovations would move through a linear process of approvals, Sander said things were very different during the pandemic, when many of the phases moved in tandem with each other instead of sequentially.&nbsp;Introducing&nbsp;health technology assessment&nbsp;earlier into the&nbsp;process of innovation&nbsp;would&nbsp;also&nbsp;help&nbsp;speed up the adoption of new technologies, Sander said.</p> <p>At the pre-clinical stage, Sander said, provinces and territories were already planning vaccine rollouts. Health Canada accepted vaccine data on a rolling basis&nbsp;and data was shared with relevant parties much earlier than it normally would be.</p> <p>“I hope that some of those characteristics will be maintained&nbsp;– [for instance] parallel review and not having to wait until each step is finished.”</p> <p>Beaudry said COVID-19 demonstrated the importance of the government playing an active role in the innovation ecosystem.</p> <p>“We need to de-silo the economy because innovation very often is a combination of knowledge from multiple disciplines and multiple sectors. With COVID the government has been forced to do that really quickly. We need to draw the lessons in terms of cross-sector cross agency collaboration.”</p> <h4>Support for new companies and access to risk capital play a large role</h4> <div class="image-with-caption right"> <div><img alt="&quot;&quot;" src="/sites/default/files/2023-04/MMay_DSC6581_2019.jpeg" style="width: 200px; height: 237px;"><em><span style="font-size:12px;">Michael May</span></em></div> </div> <p>For smaller companies to thrive in the bioinnovation&nbsp;ecosystem, collaboration is an important element, said&nbsp;<strong>Michael May</strong>, president and chief executive officer at&nbsp;CCRM (formerly the Centre for Commercialization of Regenerative Medicine).</p> <p>“It’s about alignment of interests. Bringing groups together and understanding the common goal and focusing on that common goal. And it’s a recognition that multiple partners are required for success,” said May. “It’s amazing how much translation and commercialization get stopped by innovators feeling like they have to do it all on their own.”</p> <p>Aside from collaborations, May said, financial resources play a large role. May contrasted the Canadian ecosystem with the ecosystem in Boston, which is well known for its biotechnology sector and has more access to capital.</p> <p>“We get bogged down without the financial resources to bring people together … and we’re trying to fill gaps without those resources. [The CCRM model] was built on the premise that we needed to leverage small successes and infrastructure and investments over time to enable access to capital.”</p> <p>Walt, who has founded or co-founded several life sciences start-ups including multi-billion dollar biotech ventures Illumina, Inc. and Quanterix Corp., agreed that support for small companies is crucial.&nbsp;</p> <p>“The small companies are at the core of innovation,” he said. “That’s where invention happens; that’s where all the creativity starts.”</p> <p>Walt added that Boston and Canadian hubs like Toronto have many similarities. The biotech ecosystem in Boston started because there was a recognition that there was invention and innovation at the universities.</p> <p>“[In Canada], there are great hubs where there’s concentrations of universities. That’s where most of these ecosystems start. They start with the intellectual capital, then they attract the venture capital, and then they attract more, and it just becomes a self-fulfilling enterprise.”</p> </div> <div class="field field--name-field-news-home-page-banner field--type-boolean field--label-above"> <div class="field__label">News home page banner</div> <div class="field__item">Off</div> </div> Wed, 05 Jan 2022 17:06:42 +0000 Christopher.Sorensen 301109 at Researchers working on injection-free cell therapy for diabetes /news/researchers-working-injection-free-cell-therapy-diabetes <span class="field field--name-title field--type-string field--label-hidden">Researchers working on injection-free cell therapy for diabetes</span> <div class="field field--name-field-featured-picture field--type-image field--label-hidden field__item"> <img loading="eager" srcset="/sites/default/files/styles/news_banner_370/public/2023-04/diabetes-composite.jpeg?h=afdc3185&amp;itok=TVZzAhQt 370w, /sites/default/files/styles/news_banner_740/public/2023-04/diabetes-composite.jpeg?h=afdc3185&amp;itok=D7643X0r 740w, /sites/default/files/styles/news_banner_1110/public/2023-04/diabetes-composite.jpeg?h=afdc3185&amp;itok=GfYJXJ0i 1110w" sizes="(min-width:1200px) 1110px, (max-width: 1199px) 80vw, (max-width: 767px) 90vw, (max-width: 575px) 95vw" width="740" height="494" src="/sites/default/files/styles/news_banner_370/public/2023-04/diabetes-composite.jpeg?h=afdc3185&amp;itok=TVZzAhQt" alt="Juan Carlos Zúñiga-Pflücker and Sarah Crome"> </div> <span class="field field--name-uid field--type-entity-reference field--label-hidden"><span>Christopher.Sorensen</span></span> <span class="field field--name-created field--type-created field--label-hidden"><time datetime="2021-12-17T15:40:18-05:00" title="Friday, December 17, 2021 - 15:40" class="datetime">Fri, 12/17/2021 - 15:40</time> </span> <div class="clearfix text-formatted field field--name-field-cutline-long field--type-text-long field--label-above"> <div class="field__label">Cutline</div> <div class="field__item"><p>Juan Carlos Zúñiga-Pflücker and Sarah Crome are among the researchers working on generating pancreatic cells that can be transplanted to diabetes patients without being destroyed by their immune systems (photos courtesy of Medicine by Design)</p> </div> </div> <div class="field field--name-field-author-reporters field--type-entity-reference field--label-hidden field__items"> <div class="field__item"><a href="/news/authors-reporters/julie-crljen" hreflang="en">Julie Crljen</a></div> </div> <div class="field field--name-field-topic field--type-entity-reference field--label-above"> <div class="field__label">Topic</div> <div class="field__item"><a href="/news/topics/our-community" hreflang="en">Our Community</a></div> </div> <div class="field field--name-field-story-tags field--type-entity-reference field--label-hidden field__items"> <div class="field__item"><a href="/news/tags/institute-biomedical-engineering" hreflang="en">Institute of Biomedical Engineering</a></div> <div class="field__item"><a href="/news/tags/insulin-100" hreflang="en">Insulin 100</a></div> <div class="field__item"><a href="/news/tags/princess-margaret-cancer-centre" hreflang="en">Princess Margaret Cancer Centre</a></div> <div class="field__item"><a href="/news/tags/sunnybrook-health-sciences" hreflang="en">Sunnybrook Health Sciences</a></div> <div class="field__item"><a href="/news/tags/temerty-faculty-medicine" hreflang="en">Temerty Faculty of Medicine</a></div> <div class="field__item"><a href="/news/tags/toronto-general-hospital" hreflang="en">Toronto General Hospital</a></div> <div class="field__item"><a href="/news/tags/resarch-innovation" hreflang="en">Resarch &amp; Innovation</a></div> <div class="field__item"><a href="/news/tags/medicine-design" hreflang="en">Medicine by Design</a></div> <div class="field__item"><a href="/news/tags/stem-cell" hreflang="en">Stem Cell</a></div> <div class="field__item"><a href="/news/tags/university-health-network" hreflang="en">University Health Network</a></div> </div> <div class="clearfix text-formatted field field--name-body field--type-text-with-summary field--label-hidden field__item"><p>In a person with type 1 diabetes, the body mistakenly attacks pancreatic cells that produce insulin, a hormone responsible for regulating blood sugar.</p> <p>Without insulin, serious and eventually fatal symptoms will occur. Yet,&nbsp;imagine if, instead of needing daily insulin injections, people with diabetes could have insulin-producing cells placed back into the body, fixing the problem at its source. This is the vision of a Medicine by Design-funded research team.</p> <p>The approach is not without its challenges.</p> <p>“Scientists are able to generate pancreatic cells from stem cells in the lab, and they can be transplanted to someone who has lost pancreatic function, but they’ll be reattacked by the immune system,” says&nbsp;<strong>Juan-Carlos Zúñiga-Pflücker</strong>, senior scientist at Sunnybrook Research Institute and professor of immunology in the Temerty Faculty of Medicine. “What our work is meant to do is enable those transplants to be broadly acceptable so anyone can benefit from transplanted therapies. But the barrier of the immune system is a difficult thing to overcome, and even more so in the context of autoimmunity.”</p> <p>The cells are attacked because the immune system recognizes them as harmful invaders instead of helpful therapies. It is a complex problem that demands a complex strategy – and that strategy is an emerging area of research called immunoengineering, which uses bioengineering techniques to manipulate the immune system.</p> <p>The only way to currently suppress the immune system is through drug treatments, but they’re not selective; they suppress the whole immune system and leave people vulnerable to infection and illness.</p> <p>The team’s strategy aims to be more precise. They want to finely tune the immune system to maintain a healthy system while not rejecting a therapeutic transplant.</p> <p>Zúñiga-Pflücker says a collaborative effort is important in solving this major challenge to regenerative medicine. “We can optimize cell types and engineer effective tissues in our separate labs. But if we don’t come together to create better tools to engineer the immune system, these therapies will not be usable. It’s something very fundamental.”</p> <p>The team&nbsp;is&nbsp;<a href="https://mbd.utoronto.ca/research/research-portfolio/">one of 12 sharing nearly $21 million in funding</a>&nbsp;from Medicine by Design over three years. Funded by a $114-million grant from the Canada First Research Excellence Fund, Medicine by Design is a strategic research initiative that is working at the convergence of engineering, medicine and science to catalyze transformative discoveries in regenerative medicine and accelerate them toward clinical impact.</p> <p>Though the research could be applied broadly across regenerative medicine therapies, type 1 diabetes makes an ideal test case, says Zúñiga-Pflücker, who is also chair of the department of immunology.</p> <p>“Not only is diabetes an autoimmune disease, where the diabetic’s own immune system attacks and kills insulin producing cells, but attempts to replace the lost cells with transplanted cells are also challenged by other impacts of the disease, as well as the presence of auto-reactive immune cells,” he says. “This makes it a powerful test case for our research since we can test the transplants under multiple immune stresses.”</p> <p>Zúñiga-Pflücker leads the project, which brings the work of six different labs together.</p> <p>Two labs, led by the Temerty Faculty of Medicine’s&nbsp;<strong>Maria Cristina Nostro</strong>, a senior scientist at the University Health Network’s (UHN) McEwen Stem Cell Institute; and&nbsp;<strong>Sara Nunes Vasconcelos</strong>, a scientist at UHN’s Toronto General Hospital Research Institute, are using stem cells to generate tissues containing insulin-secreting cells for transplants.</p> <p>Zúñiga-Pflücker says that this arm of the project is well ahead of schedule. “The Nostro and Vasconcelos labs are defining the right conditions that are necessary for generating insulin-producing cells, which are called islet cells. They’re creating newer and more effective ways to make these tissues.”</p> <p>Nostro and Vasconcelos are also associate professors at U of T in&nbsp;the department of physiology and Institute of Biomedical Engineering, respectively.</p> <p>The tissues created in their labs will be used to test the work of the other four labs involved in the project, which are concerned with engineering the immune reaction. And here, each of these labs is bringing a piece of the puzzle.</p> <h3><a href="/news/cloaking-technology-helping-therapeutic-cells-evade-your-immune-system">Read about research into therapeutic cell “cloaking”</a></h3> <p>Zúñiga-Pflücker and&nbsp;<strong>Naoto Hirano</strong>, a senior scientist at Princess Margaret Cancer Centre and a professor of immunology at U of T, work on producing regulatory T cells (Tregs). These cells can supress immune response&nbsp;and play a role in preventing autoimmune diseases like diabetes.</p> <p>In earlier Medicine by Design-funded research,&nbsp;Zúñiga-Pflücker and Hirano&nbsp;<a href="https://pubmed.ncbi.nlm.nih.gov/30552102/">came up with a method for producing T cells in a defined way</a>. Some of the key breakthroughs developed as part of this research helped lay the foundation for&nbsp;Notch Therapeutics, a company co-founded by Zúñiga-Pflücker,&nbsp;<a href="https://mbd.utoronto.ca/news/notch-therapeutics-closes-85-million-series-a-financing/">which&nbsp;closed an $85-million (U.S.) Series A financing earlier this year</a>.</p> <p>Now, in the current research project, the two labs are crafting methods for producing Tregs and investigating how harnessing the power of other types of immune cells to work alongside the Tregs can induce the immune system to tolerate transplanted therapies.</p> <p>The third investigator is&nbsp;<strong>Tracy McGaha</strong>, whose lab is looking at the role of macrophages, a type of white blood cell that that typically helps to attack foreign substances but can also play a role in repairing damaged tissues. McGaha is a senior scientist at Princess Margaret Cancer Centre, UHN, and a professor in the department of immunology in the Temerty Faculty of Medicine.</p> <p>A fourth lab, led by&nbsp;<strong>Sarah Crome</strong>, is investigating a family of immune cells called innate lymphoid cells (ILCs), which act within tissues to help induce and modulate immune responses.</p> <p>“We know several immune cell populations we individually study can protect from harmful immune responses and promote immune tolerance,” says Crome, who is a scientist at the Toronto General Hospital Research Institute, UHN, and an assistant professor of immunology at U of T. “The trouble is when you get into a situation that combines an autoimmune disease with rejection that can occur following islet transplantation, it’s a real challenge shutting down multiple harmful and sustained immune responses.”</p> <p>Crome says that there are many different types of ILCs, so her work focuses on narrowing down which types of ILCs are best to use along with the Tregs.</p> <p>Right now, each of the four labs working with immune cells are optimizing their cell types and techniques, and then, Crome says they will bring all their “best players” together.</p> <p>“We’re really looking at harnessing whole networks of cells, instead of just looking at one cell population at a time. It’s bringing all of our collective expertise together into one project that makes this a powerful approach.”</p> <p>Zúñiga-Pflücker says Medicine by Design has been instrumental in uniting this team of experts.</p> <p>“Thanks to Medicine by Design’s support of our immunoenigneering program, we’re able to bring together multiple research sites within the Ƶ and affiliated research institutes; UHN’s Princess Margaret Cancer Centre, Toronto General Hospital Research Institute and McEwen Stem Cell Institute; and Sunnybrook Research Institute.”</p> </div> <div class="field field--name-field-news-home-page-banner field--type-boolean field--label-above"> <div class="field__label">News home page banner</div> <div class="field__item">Off</div> </div> Fri, 17 Dec 2021 20:40:18 +0000 Christopher.Sorensen 301217 at Medicine by Design-funded researchers generate cells to treat bile duct disorders resulting from cystic fibrosis /news/medicine-design-funded-researchers-generate-cells-treat-bile-duct-disorders-resulting-cystic <span class="field field--name-title field--type-string field--label-hidden">Medicine by Design-funded researchers generate cells to treat bile duct disorders resulting from cystic fibrosis</span> <div class="field field--name-field-featured-picture field--type-image field--label-hidden field__item"> <img loading="eager" srcset="/sites/default/files/styles/news_banner_370/public/2023-04/Cholangiocyte%20monolater%20Zo-1%20Primary%20cilia%20copy%20feature%20image-crop.jpeg?h=afdc3185&amp;itok=7a23GO0V 370w, /sites/default/files/styles/news_banner_740/public/2023-04/Cholangiocyte%20monolater%20Zo-1%20Primary%20cilia%20copy%20feature%20image-crop.jpeg?h=afdc3185&amp;itok=RJThgtNi 740w, /sites/default/files/styles/news_banner_1110/public/2023-04/Cholangiocyte%20monolater%20Zo-1%20Primary%20cilia%20copy%20feature%20image-crop.jpeg?h=afdc3185&amp;itok=rrnbAvXj 1110w" sizes="(min-width:1200px) 1110px, (max-width: 1199px) 80vw, (max-width: 767px) 90vw, (max-width: 575px) 95vw" width="740" height="494" src="/sites/default/files/styles/news_banner_370/public/2023-04/Cholangiocyte%20monolater%20Zo-1%20Primary%20cilia%20copy%20feature%20image-crop.jpeg?h=afdc3185&amp;itok=7a23GO0V" alt="Cholangiocyte monolater"> </div> <span class="field field--name-uid field--type-entity-reference field--label-hidden"><span>Christopher.Sorensen</span></span> <span class="field field--name-created field--type-created field--label-hidden"><time datetime="2021-11-22T12:23:18-05:00" title="Monday, November 22, 2021 - 12:23" class="datetime">Mon, 11/22/2021 - 12:23</time> </span> <div class="clearfix text-formatted field field--name-field-cutline-long field--type-text-long field--label-above"> <div class="field__label">Cutline</div> <div class="field__item"><p>An image of the bile duct cells, or cholangiocytes, derived from stem cells (Image courtesy of Mina Ogawa)</p> </div> </div> <div class="field field--name-field-author-reporters field--type-entity-reference field--label-hidden field__items"> <div class="field__item"><a href="/news/authors-reporters/julie-crljen" hreflang="en">Julie Crljen</a></div> </div> <div class="field field--name-field-topic field--type-entity-reference field--label-above"> <div class="field__label">Topic</div> <div class="field__item"><a href="/news/topics/breaking-research" hreflang="en">Breaking Research</a></div> </div> <div class="field field--name-field-story-tags field--type-entity-reference field--label-hidden field__items"> <div class="field__item"><a href="/news/tags/temerty-faculty-medicine" hreflang="en">Temerty Faculty of Medicine</a></div> <div class="field__item"><a href="/news/tags/graduate-students" hreflang="en">Graduate Students</a></div> <div class="field__item"><a href="/news/tags/hospital-sick-children" hreflang="en">Hospital for Sick Children</a></div> <div class="field__item"><a href="/news/tags/medicine-design" hreflang="en">Medicine by Design</a></div> <div class="field__item"><a href="/news/tags/research-innovation" hreflang="en">Research &amp; Innovation</a></div> <div class="field__item"><a href="/news/tags/stem-cells" hreflang="en">Stem Cells</a></div> <div class="field__item"><a href="/news/tags/university-health-network" hreflang="en">University Health Network</a></div> </div> <div class="clearfix text-formatted field field--name-body field--type-text-with-summary field--label-hidden field__item"><p>Researchers at the Ƶ and its partner hospitals have discovered a way to generate functional cells from stem cells that could open new treatment avenues for people with cystic fibrosis who have liver disease.</p> <p>Funded by Medicine by Design and completed with&nbsp;the collaborative efforts of multiple labs, the research was&nbsp;recently <a href="https://www.nature.com/articles/s41467-021-26764-0">published in&nbsp;</a><em><a href="https://www.nature.com/articles/s41467-021-26764-0">Nature Communications</a>.</em></p> <p>While cystic fibrosis is&nbsp;well known as a lung disease, the second most common cause of death in patients is actually liver disease. This is because people with cystic fibrosis can experience a decrease in the flow of bile fluid, which is secreted by the liver that helps with digestion and detoxification. The bile duct is a tube-like structure found in the liver that carries bile to the small intestine. The loss of flow leads to liver dysfunction. As a result, some patients require liver transplantation.</p> <div class="image-with-caption left"> <div><img alt="Shinichiro Ogawa" class="media-element file-media-original lazy" data-delta="1" height="320" loading="lazy" src="/sites/default/files/2023-04/Shin%20Ogawa.jpeg" typeof="foaf:Image" width="141"><em>Shinichiro Ogawa</em></div> </div> <p>“Until now, we have not had a good scientific model to study the human liver’s bile duct system physiologically,” says senior study author&nbsp;<strong>Shinichiro Ogawa</strong>, an affiliate scientist at the McEwen Stem Cell Institute and Ajmera Transplant Centre, University Health Network (UHN), and an assistant professor in U of T’s department of laboratory medicine and pathobiology.</p> <p>“In order to study a disease in a dish at the basic cellular and molecular level, we need functional cells. The fact that we can derive these functional cells from stem cells gives us a totally different way of evaluating and treating defective cells.”</p> <p>The cells that the researchers generated have the properties of mature, functional cholangiocyte cells, which are the cells that make up the bile duct. Cholangiocytes play a role in several chronic and progressive liver diseases that have few medical treatment options. These diseases are responsible for about 20 per cent of adult liver transplants and most pediatric liver transplants. ​</p> <p>Not much is known about the bile duct disorders that can lead to liver disease, but Ogawa says this research may lead to a deeper understanding of the specific mechanisms of the disease, as well as being a powerful tool for finding new treatments.</p> <p>Ultimately, the researchers say it may be possible to develop therapies that involve transplanting the cells into a patient who has bile duct disease, bypassing the need for a transplant.</p> <p>The work is funded through Medicine by Design’s large team projects. Ogawa and his co-investigator&nbsp;<strong>Christine Bear</strong>, a senior scientist in molecular medicine at The Hospital for Sick Children and a U of T professor of physiology,&nbsp;are part of a team focused on harnessing the liver’s power to regenerate.</p> <p>Funded by a $114-million grant from the Canada First Research Excellence Fund, Medicine by Design is a strategic research initiative at U of T and its affiliated hospitals that is working at the convergence of engineering, medicine and science to catalyze transformative discoveries in regenerative medicine and accelerate them toward clinical impact.</p> <p>Ogawa says it was the work of many different researchers and labs that brought the study together.</p> <p>Beginning with pluripotent stem cells, which have the capacity to give rise to most of the cell types in the human body,&nbsp;<strong>Mina Ogawa</strong>, scientific associate at the McEwen Stem Cell Institute, was able to identify methods to efficiently guide the stem cells through the process of changing into cholangiocytes.&nbsp;<strong>Donghe Yang</strong>&nbsp;– a PhD candidate in the lab of&nbsp;<strong>Gordon Keller</strong>, who is director of UHN’s McEwen Stem Cell Institute – analyzed the stem cell-derived cholangiocytes at a single cell level to compare to human cholangiocytes in the liver.</p> <p>The team used&nbsp;earlier <a href="/news/u-t-researchers-involved-first-map-human-liver-cells-molecular-level">Medicine by Design-funded research on the Human Liver Map</a>&nbsp;to confirm that the cells they developed had the characteristics of mature cells, which are more functional and have more therapeutic applications as opposed to immature cells.</p> <p>Researchers in Bear’s lab&nbsp;– <strong>Janet (Jia-Xin) Jiang</strong>, research project co-ordinator, and&nbsp;<strong>Sunny Xia</strong>, PhD student – were able to demonstrate that the cells were functional and responded to natural environmental cues like the force associated with fluid transport. Their work also showed that newly developed stem cell-derived cholangiocytes could, in the future, play a powerful role in developing organ-specific therapies.</p> <p>“These studies highlight the importance of generating mature cells from stem cells that faithfully mimic the functional properties of the native tissue,” says Bear. “We can better understand the real effect of disease-causing mutations and cystic fibrosis therapies, especially in those hard-to-access organs”.</p> <p>Bear adds that this work was made possible through an interdisciplinary effort. “This work is an excellent example of how collaboration among the research teams funded by Medicine by Design can help to target cutting-edge basic research in a way that will make a difference for patients.”</p> <p>Ogawa says the power of stem cell technology is to be able to identify and correct the disease at a cellular level. One day, this research could lead to the development of personalized, customized treatments for other bile duct disorders. Ogawa adds that the McEwen Stem Cell Institute is a world leader in producing different cell types from these stem cells.</p> </div> <div class="field field--name-field-news-home-page-banner field--type-boolean field--label-above"> <div class="field__label">News home page banner</div> <div class="field__item">Off</div> </div> Mon, 22 Nov 2021 17:23:18 +0000 Christopher.Sorensen 301219 at Cloaking technology: Helping therapeutic cells evade your immune system /news/cloaking-technology-helping-therapeutic-cells-evade-your-immune-system <span class="field field--name-title field--type-string field--label-hidden">Cloaking technology: Helping therapeutic cells evade your immune system</span> <div class="field field--name-field-featured-picture field--type-image field--label-hidden field__item"> <img loading="eager" srcset="/sites/default/files/styles/news_banner_370/public/DrAndrasNagy-crop.jpg?h=afdc3185&amp;itok=9mAylvnl 370w, /sites/default/files/styles/news_banner_740/public/DrAndrasNagy-crop.jpg?h=afdc3185&amp;itok=c6IMEoI0 740w, /sites/default/files/styles/news_banner_1110/public/DrAndrasNagy-crop.jpg?h=afdc3185&amp;itok=8IS2etXa 1110w" sizes="(min-width:1200px) 1110px, (max-width: 1199px) 80vw, (max-width: 767px) 90vw, (max-width: 575px) 95vw" width="740" height="494" src="/sites/default/files/styles/news_banner_370/public/DrAndrasNagy-crop.jpg?h=afdc3185&amp;itok=9mAylvnl" alt="Andras Nagy"> </div> <span class="field field--name-uid field--type-entity-reference field--label-hidden"><span>lanthierj</span></span> <span class="field field--name-created field--type-created field--label-hidden"><time datetime="2021-10-08T06:57:51-04:00" title="Friday, October 8, 2021 - 06:57" class="datetime">Fri, 10/08/2021 - 06:57</time> </span> <div class="clearfix text-formatted field field--name-field-cutline-long field--type-text-long field--label-above"> <div class="field__label">Cutline</div> <div class="field__item">Andras Nagy (Photo provided by Sinai Health Foundation)</div> </div> <div class="field field--name-field-author-reporters field--type-entity-reference field--label-hidden field__items"> <div class="field__item"><a href="/news/authors-reporters/paul-fraumeni" hreflang="en">Paul Fraumeni</a></div> </div> <div class="field field--name-field-topic field--type-entity-reference field--label-above"> <div class="field__label">Topic</div> <div class="field__item"><a href="/news/topics/breaking-research" hreflang="en">Breaking Research</a></div> </div> <div class="field field--name-field-story-tags field--type-entity-reference field--label-hidden field__items"> <div class="field__item"><a href="/news/tags/institute-biomedical-engineering" hreflang="en">Institute of Biomedical Engineering</a></div> <div class="field__item"><a href="/news/tags/institutional-strategic-initiatives" hreflang="en">Institutional Strategic Initiatives</a></div> <div class="field__item"><a href="/news/tags/insulin-100" hreflang="en">Insulin 100</a></div> <div class="field__item"><a href="/news/tags/temerty-faculty-medicine" hreflang="en">Temerty Faculty of Medicine</a></div> <div class="field__item"><a href="/news/tags/toronto-general-hospital" hreflang="en">Toronto General Hospital</a></div> <div class="field__item"><a href="/news/tags/diabetes" hreflang="en">Diabetes</a></div> <div class="field__item"><a href="/news/tags/medicine-design" hreflang="en">Medicine by Design</a></div> <div class="field__item"><a href="/news/tags/mount-sinai-hospital" hreflang="en">Mount Sinai Hospital</a></div> <div class="field__item"><a href="/news/tags/research-innovation" hreflang="en">Research &amp; Innovation</a></div> <div class="field__item"><a href="/news/tags/stem-cells" hreflang="en">Stem Cells</a></div> <div class="field__item"><a href="/news/tags/university-health-network" hreflang="en">University Health Network</a></div> </div> <div class="clearfix text-formatted field field--name-body field--type-text-with-summary field--label-hidden field__item"><p>Stem cell pioneer <b>Andras Nagy</b> has a way of describing the work of your immune system: “It’s surveillance inside our body.”</p> <p>That surveillance does us good when harmful bacteria or viruses enter our body. The immune system releases fighter cells to kill the invaders.</p> <p>But regenerative medicine therapies often involve transplanting tissues or cells into a person. When new heart or pancreatic cells are transplanted, for example, the immune system will see these good things as enemies and reject them. Drug treatment can be used to suppress this immune response, but it can leave the person open to serious infection.</p> <p>Nagy, a professor in the department of obstetrics and gynaecology at the Ƶ's Temerty Faculty of Medicine and a senior investigator at Sinai Health System’s Lunenfeld-Tanenbaum Research Institute, and his research team have been experimenting with a process called “cloaking,” which he believes could be used to hide therapeutic cells from the immune surveillance system and allow them to do their good work.</p> <p>Though this research will one day be applicable to all cell therapies, Nagy’s team is currently testing the cloaking technology with insulin-secreting pancreatic cells that are made from stem cells and could be a powerful cell therapy for type 1 diabetes.</p> <p>Stem cells are cells that can be reprogrammed and turned into an unlimited source of any type of human cell needed for treatment. Nagy notes that the first years of stem cell research were at the basic science level, as scientists worked to understand the nature of stem cells. He says about 10 years ago, there was a notable shift to what he calls <a href="https://tri.uams.edu/about-tri/what-is-translational-research/">“translational”</a> research. His work is part of this wave of applied science; in fact, in 2015 he co-founded a biotech company, <a href="https://pancella.com/">panCELLa Inc.</a>, to make his cell technologies widely available.</p> <p>“Regenerative medicine is at a point now where we can translate our research into therapies that can help all humankind,” he says.</p> <p>The Canada Research Chair in Stem Cells and Regeneration, Nagy says that researchers have long known that transplanted cells and tissues can be attacked by the immune system.</p> <p>“We wondered if there was a way to hide or ‘cloak’&nbsp;these good cells, so the immune response wouldn’t destroy them,” says Nagy. “But before we could move into that we had to deal with a significant hurdle – the safety of the implanted cells.”</p> <p>Nagy points out that when these new cells are created, there is a chance they could mutate and become cancerous. The more cells needed for a therapy, the more cell divisions that take place, meaning a higher chance of mutation and cancer.</p> <p>In earlier research, partially funded by a previous Medicine by Design team projects award, Nagy published a <a href="https://www.nature.com/articles/s41586-018-0733-7" target="_blank">paper in <i>Nature</i></a> that described a “fail safe” cell technology that he and his team devised that can increase the safety of a cell graft and has a formula to quantify the risk of mutation so that people can make an informed decision on whether such a risk is acceptable to them.</p> <p>The fail-safe system is a switch that eliminates potentially dangerous cells during cell therapy. The switch is introduced into stem cells, which are then turned into the therapeutic cells. The switch is turned on by a drug that can be added to the cell graft or applied directly into the body after transplant.</p> <p>Nagy says the killer switch is fail safe because it is composed of two genes, one required for division and one that can trigger cell suicide, stitched together. If a mutated gene begins dividing, the drug is there to activate the kill switch and kill the cell. And if the cell loses the switch, it also loses the ability to multiply.</p> <p>With the important first step of creating the fail safe switch done, Nagy turned to the cloaking, work that is supported by his team’s current Medicine by Design team projects award.</p> <p>Nagy’s team is <a href="https://mbd.utoronto.ca/research/funded-initiatives/team-projects-cycle-2/">one of 12 sharing nearly $21 million in funding</a> from Medicine by Design over three years. Funded by a $114-million grant from the <a href="https://www.cfref-apogee.gc.ca/home-accueil-eng.aspx" target="_blank">Canada First Research Excellence Fund</a>, Medicine by Design is an <a href="https://isi.utoronto.ca/institutional-strategic-initiatives-are-cross-divisional-research-networks-pursuing-grand-challenges-and-bold-ideas-that-require-true-collaboration-and-the-integration-of-various-disciplinary-research/initiatives/">institutional strategic research initiative </a>that is working at the convergence of engineering, medicine and science to catalyze transformative discoveries in regenerative medicine and accelerate them toward clinical impact.</p> <p>“Medicine by Design has been really important in supporting scientists in bringing the possibilities of regenerative medicine to patients. I’m grateful to Medicine by Design for funding the high-risk and high impact projects that many other funding agencies often say are just too ambitious.”</p> <p>The cloaking technology involves turning off certain genetic switches in the cells created from stem cells to avoid detection by the immune system. This work was supported by findings from&nbsp;<a href="https://mbd.utoronto.ca/news/medicine-by-design-funded-researchers-devise-new-strategy-to-improve-the-safety-of-cell-therapies/" target="_blank">a devastating cancer found in Tasmanian devils</a>, the marsupial native to the Australian state of Tasmania.</p> <p>Between 1996 and 2015, 95 per cent of the Tasmanian devil population was wiped out as a result of contagious facial cancer cells transmitted when the devils bit each other. Nagy’s research found that the cancer had a way of cloaking itself from the devils’ immune system, which backed up his theory that cells could be hidden from the immune system.</p> <p>Nagy identified eight genes that are central to immunity. He reasoned that just as the Tasmanian devils’ facial cancer could avoid detection by turning off the right genetic switches, his stem cell-derived cells could similarly become cloaked. Scientists in Nagy lab have been testing the cloaking in mice with encouraging results.</p> <div class="image-with-caption left"> <div><img class="migrated-asset" src="/sites/default/files/Sara%20V-crop.jpg" alt><em><span style="font-size:12px;">Sara Vasconcelos</span></em></div> </div> <p>Working with Nagy are <b>Maria Cristina Nostro</b>, senior scientist at the University Health Network’s (UHN) McEwen Stem Cell Institute and associate professor, department of physiology at U of T; and <b>Sara Vasconcelos</b>, scientist at the UHN’s Toronto General Hospital Research Institute and associate professor at U of T’s Institute of Biomedical Engineering.</p> <p>The Nostro lab’s focus is to generate insulin-secreting pancreatic cells from stem cells. These cells could one day have the potential to treat patients with type 1 diabetes. Nostro works closely with Vasconcelos, whose lab focuses on helping to keep the transplanted cells alive once they enter the body. Cells need oxygen and other nutrients, which are delivered through the blood vessels.</p> <p>Together, the team is testing ways to integrate Nagy’s technologies into Nostro’s functional pancreatic cells. Vasconcelos’s aim is for these therapies to survive in the body.</p> <p>“When you just transplant the cells, they don’t have blood vessels, so they’ll die, independent of whether the immune system kills them or not. If they die, we’ll never know if it was the immune system or lack of oxygen,” Vasconcelos says. The Vasconcelos lab team <a href="https://mbd.utoronto.ca/news/insulin-cells-with-blood-vessels/" target="_blank">repurposes small vessels</a>, which exist in fat. They then use the vessels as units to increase blood flow and allow the cells to engraft and survive after they have been transplanted.</p> <p>Nagy says the combination of the fail safe and cloaking technologies will make for a powerful therapy. “On the one hand, we can now introduce good cells into recipient’s body that can be hidden from the immune response and do the work they were intended to do. And that means doctors won’t have to use immunosuppression drugs. Finally, if one of the newly created cells is cancerous to the patient, our safe-cell technology can kill it or at least give us information on risk that we can communicate to the patient.”</p> <p>When stem cell-derived therapies are created for individual patients, Nagy says, it is expensive, costing hundreds of thousands of dollars per patient. Nagy envisions turning his cells that combine fail safe and immune cloaking technologies into “off-the-shelf” products that can be used by anyone and are inexpensive.</p> <p>Nagy has been building a notable research career in regenerative medicine since he came to Canada from Hungary in 1989, initially joining the lab of renowned researcher and <a href="https://www.provost.utoronto.ca/awards-funding/university-professors/">University Professor&nbsp;</a><b>Janet Rossant </b>at the Samuel Lunenfeld Research Institute (now the Lunenfeld-Tannenbaum Research Institute) at Mount Sinai Hospital.</p> </div> <div class="field field--name-field-news-home-page-banner field--type-boolean field--label-above"> <div class="field__label">News home page banner</div> <div class="field__item">Off</div> </div> Fri, 08 Oct 2021 10:57:51 +0000 lanthierj 170742 at