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Microscale Tissue Engineering Strategies for Therapeutic Applications

Dr. Mark Ungrin, Assistant Professor, University of Calgary

Introduction: A central challenge for cell-based therapies is the method of delivery. While injection of single-cell suspensions is attractive from the perspectives of cost, ease of access and minimal invasiveness, it is subject to several challenges. Cells often die and / or fail to engraft, and can enter the bloodstream and become mis-localized. We hypothesize that injection of microtissues – engineered assemblies of one or more cell types with or without exogenous biomaterials – will provide a broadly useful resolution to these challenges. Our objective is to demonstrate the effectiveness of this approach in the treatment of type I diabetes. Materials and Methods: We employ my widely-used AggreWell technology for cellular aggregation to form engineered pseudoislets, optimize their behavior, and assess their performance in vitro (survival, gene expression, glucose-stimulated insulin secretion) and in vivo (restoration of normoglycemia in diabetic mice). Results: By modulating the size and formation conditions of the pseudoislets, we have identified conditions that result in several-fold improved performance over native islets in vitro. Preliminary transplant experiments indicate the pseudoislets are able to very effectively restore normoglycemia; quantitative studies are underway to more precisely establish a comparison with conventional islet transplants. Discussion and Conclusions: We demonstrate a therapeutically relevant advance in the preparation of materials for cell-based therapy for type I diabetes, and in the process establish a generalizable strategy for the generation and optimization of therapeutically relevant microtissues.

 

About the Speaker…

Dr. Ungrin joined the University of Calgary in 2012 as Assistant Professor in Comparative Biology and Experimental Medicine in the Faculty of Veterinary Medicine. He is an interdisciplinary researcher, with an undergraduate degree in Biochemistry, a PhD in Medical Biophysics (Cellular and Molecular Biology), postdoctoral training in Stem Cell Bioengineering, and work experience in the pharmaceutical industry (Merck). His academic research program is funded by both NSERC and CIHR (among other sources), and includes microscale tissue engineering, stem cell biology, 3D printing and technology development.

He is also interested in improving the way research is carried out – a research program can be considered as a machine for converting resources into new knowledge, so how can we make that machine as efficient as possible? These efforts have led to the establishment of new research tools, including the AggreWell technology, now translated to a successful commercial product in partnership with Stem Cell Technologies of Vancouver. This system has been referenced in over 350 publications, from every continent except Antarctica. It is in use in a broad range of applications around the world, including chondrogenesis from mesenchymal stem cells (Australia), standardized generation of neural precursors from pluripotent stem cells (United States), toxicological analyses in hepatocytes (Denmark), trophoblast implantation studies (China), detailed studies of tumour spheroids (United States), and assessment of spinal cord regeneration in salamanders (Germany).


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