Medicine by Design Symposium
Each year, members in our learning community have the opportunity to attend the Medicine by Design Symposium, a local conference about Stem Cells and regenerative medicine. Our goal is to present this knowledge in an easy-to-understand and accessible manner for all those who are interested. Explore the 2024 conference highlights below!
Photo retrieved from: https://mbd.utoronto.ca/news/9th-symposium-in-pictures/#
Sonya MacParland: Targeting Resident Liver Immunity to Treat Hepatic Disease
Written by: Dushana Stefanovici
Dr. Sonya MacParland is one of the leading scientists discussing the importance of regenerative medicine in healthcare and research. As a researcher at the Amera Transplant center at the University Health Network (UHN) in Toronto, ON, she addressed the priority for reaching a goal where regenerative medicine can be another medical treatment to patients whose only available option is a transplant.
Her talk discusses the importance of defining a diseased liver and expanding our understanding of a healthy liver – by creating a liver map! She uses primary sclerosing cholangitis (PSC) a rare chronic liver disease, as an example of this advancement in action. PSC is understudied, with no known cause or treatment – thought to be auto-immune mediated with an underlying genetic component. Generally, PSC is defined by inflammation and scarring of the bile ducts, resulting in bile buildup which causes further liver damage. MacParland introduces a multi-omic investigation of PSC and healthy livers guided by Dr. Tallulah S. Andrews (2024). Through single-cell and single-nucleus RNA sequencing, and spatial transcriptomics, they worked to profile the cellular ecosystem of PSC and normal livers. They compared activity, interactions, and localization of immune and non-immune cells in areas of high disease and revealed PSC co-expressed bile duct cell markers providing a basis for targeted novel therapies and research in hepatic inflammatory mediation.
Single-cell, single-nucleus, and spatial transcriptomics characterization of the immunological landscape of the liver will provide a foundation for single-cell liver disease studies enabling future personalized treatments that do not depend on high-risk transplants. MacParland emphasized the significant impact of this “diseased liver-map,” in conjunction with her previous work (2018) in creating a reference map at a single-cell resolution of a normal liver which has now acted as a baseline for PSC exploration and potential development of novel treatments.
You can read more about this work here:
Andrews, T. S., et al. (2024); https://doi.org/10.1016/j.jhep.2023.12.023, and MacParland, S. A., et al. (2018); https://doi.org/10.1038/s41467-018-06318-7 .
Elmar Jaeckel: Curing Type 1 Diabetes with CAR-Tregs
Written by: Dushana Stefanovici
Medical Director of the Toronto Liver Transplant Program for the Toronto University Health Network (UHN), Dr. Elmar Jaeckel, has been a part of leading research in immune tolerance and metabolic inflammation, establishing immune tolerance in type 1 diabetes, and development of new cell and gene therapies. He began his talk by stating that “the best transplant is the one you don’t have to perform” continuing the conversation of regenerative medicine and its leading significance in developing healthcare approaches.
Type 1 Diabetes (T1D) is central to his research, focusing on how, despite major advancements, there is still a high morbidity and reduced life expectancy amongst those with T1D. Dr. Jaeckel introduces his contribution in a recent development of beta cell-specific Chimeric Antigen Receptors (CAR) that work to target the antigen ectonucleoside triphosphate diphosphohydrolase 3 (ENTPD3). ENTPD3 is found at both early and progressed states of T1D on beta cells, and thus ENTPD3 CAR regulatory T cells (Tregs) were able to prevent disease progression in T1D mouse models. In addition, human ENTPD3 CAR T cells showed a stable regulatory characteristic, with significant contributions in activation and suppression, and were fully activated by human islets in culture.
This work offers an opportunity for a preventative treatment option in patients with early on-set T1D progression. By introducing ENTPD3 CAR-Tregs into these patients the hope is that this will allow for tissue-specific tolerance in the pancreas without compromising immune function. This pathway towards a novel treatment option for TD1 is promising and if successful could preserve insulin production by the patient’s own pancreas. This type of CAR-T cell and gene therapy has been effective in targeting cancer cells and this work shows promise for treatment of autoimmune diseases.
You can read more about this work here:
Pieper, T., et al. (2024); https://doi.org/10.1101/2024.11.12.622951