β-cell engineering from human pancreatic duct-derived cells
(2016)
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- Abstract
- Pancreatic epithelial cells represent an attractive cell source for replacement therapy of type 1 diabetes. In this context, we designed a protocol for expansion of human pancreatic duct-derived cells (HDDCs) and showed their β-cell engineering potential. We reprogrammed HDDCs into β-cell-like lineage by using two different strategies: cocktails of molecules that recapitulate the embryonic β-cell development and the mRNA-based overexpression of key pancreatic transcription factors (TFs). This second approach showed higher efficiency leading to a mature β-cell phenotype in vitro only after MAFA overexpression within 7 days. Glucose-responsive insulin secretion was detected in both in vitro and in vivo after transplantation in immunosuppressed diabetic mice. Although further studies are still required to observe long-term function and side effects after transplantation, this study suggests the role of HDDCs as promising candidates for diabetes cell therapy.
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Citations
Corritore, E. (2016). β-cell engineering from human pancreatic duct-derived cells. https://hdl.handle.net/2078.5/72614