Microscale Tissue Engineering for the Study and Treatment of Diabetes
Date
2018-12-12
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Abstract
Islet transplantation is a promising approach to the treatment of insulin-dependent diabetes. However, a major clinical challenge is inefficient survival and engraftment of the transplanted material. This has been associated with insufficient oxygen and nutrition delivery after loss of the endogenous capillaries, and stress induced during islet isolation and culture. Quantitative modelling of oxygen delivery predicts significant advantages for smaller islets, and consistent with this concept, smaller human islets have also performed better than larger ones in clinical settings. In order to understand and overcome these limitations for both research and clinical applications, we have established a microscale tissue engineering approach that is capable of consistently and efficiently generating size-controlled pseudoislets from human donor islets, yielding improved survival and function both in vitro and in vivo. We then combined this platform with advanced statistical methodologies and laboratory automation systems to enable assessment of large numbers of modifying factors (and their interactions) identified from the literature in parallel. This project has yielded a substantial improvement in the consistency and efficacy of islet cell packaging for transplantation, and laid a foundation for rapid transition to the clinic.
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Keywords
Islet, Transplant, Pseudoislet, Micro-tissue Engineering, Design of Experiment, Prostanoids
Citation
Yu, Y. (2018). Microscale Tissue Engineering for the Study and Treatment of Diabetes (Doctoral thesis, University of Calgary, Calgary, Canada). Retrieved from https://prism.ucalgary.ca.