Establishment of human pluripotent stem cell-derived pancreatic β-like cells in the mouse pancreas
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Author(s)
Ma, Haiting
Wert, Katherine J.
Shvartsman, Dmitry
Melton, Douglas A.
Jaenisch, Rudolf
Date Issued
February 2018
Journal
Proceedings of the National Academy of Sciences
Publisher
National Academy of Sciences (U.S.)
Citation
Ma, Haiting et al. “Establishment of Human Pluripotent Stem Cell-Derived Pancreatic β-Like Cells in the Mouse Pancreas.” Proceedings of the National Academy of Sciences 115, 15 (March 2018): 3924–3929 © 2018 National Academy of Sciences
Version
Final published version
Abstract
Type 1 diabetes is characterized by autoimmune destruction of β cells located in pancreatic islets. However, tractable in vivo models of human pancreatic β cells have been limited. Here, we generated xenogeneic human pancreatic β-like cells in the mouse pancreas by orthotopic transplantation of stem cell-derived β (SC-β) cells into the pancreas of neonatal mice. The engrafted β-like cells expressed β cell transcription factors and markers associated with functional maturity. Engrafted human cells recruited mouse endothelial cells, suggesting functional integration. Human insulin was detected in the blood circulation of transplanted mice for months after transplantation and increased upon glucose stimulation. In addition to β-like cells, human cells expressing markers for other endocrine pancreas cell types, acinar cells, and pancreatic ductal cells were identified in the pancreata of transplanted mice, indicating that this approach allows studying other human pancreatic cell types in the mouse pancreas. Our results demonstrate that orthotopic transplantation of human SC-β cells into neonatal mice is an experimental platform that allows the generation of mice with human pancreatic β-like cells in the endogenous niche. Keywords: humanized mice; human pluripotent stem cells; beta cells; diabetes
MIT Department
Massachusetts Institute of Technology. Department of Biology
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Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use.
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DOI of Published Version
https://doi.org/10.1073/PNAS.1702059115
