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Islet encapsulation to treat diabetes

Islet transplantation using the Edmonton Protocol has provided new hope for a cure for diabetes. Widespread access to this treatment would require large numbers of insulin-secreting beta cells and improved methods to avoid graft rejection. One strategy to reduce graft rejection is to place the islets inside an immunoisolation device (for example via encapsulation) that creates a physical barrier between the graft and components of the host immune system. Islet encapsulation in hydrogel beads has allowed long-term islet survival and reversal of autoimmune diabetes in non-immunosuppressed rodents. Although clinical trials in humans are ongoing, the promising results obtained in rodents have not been replicated in primates. We have developed novel emulsion- and microchannel-based methods to microencapsulate large amounts of islets within a few minutes. This new type of uncoated alginate bead could avoid issues such as fibrotic overgrowth encountered with other encapsulation technologies. Additionally, we are exploring strategies for creating vascularized macroencapsulation devices to improve oxygen and nutrient transfer within thicker grafts.

Cell encapsulation using microchannel emulsification. We have used this process to encapsulate pancreatic beta cells in alginate, and are currently adapting the process for chitosan-based encapsulation of mesenchymal stem/stromal cells. (Bitar et al., Biotechnology Process 2019)

Selected Publications:

Hoesli CA, Raghuram K, Kiang RL, Mocinecová D, Hu X, Johnson JD, Lacík I, Kieffer TJ, Piret JM. (2011) Pancreatic cell immobilization in alginate beads produced by emulsion and internal gelation. Biotechnology and Bioengineering, 108: 424-434. doi:10.1002/bit.22959

Tran R, Moraes C, Hoesli CA. (2020) Controlled clustering enhances PDX1 and NKX6.1 expression in pancreatic endoderm cells derived from pluripotent stem cells. Scientific Reports 10, 1190. doi: 10.1038/s41598-020-57787-0

Moeun BN, Ling SD, Gasparrini M, Rutman AK, Negi S, Paraskevas S, Hoesli CA. (2019) Islet Encapsulation: A Long-Term Treatment for Type 1 Diabetes. Editor: Reis, R.L. Encyclopedia of Tissue Engineering and Regenerative Medicine, Academic Press, 217-231. ISBN 9780128137000. doi: 10.1016/B978-0-12-801238-3.11135-3

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