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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America. >Establishment of human pluripotent stem cell-derived pancreatic beta-like cells in the mouse pancreas
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Establishment of human pluripotent stem cell-derived pancreatic beta-like cells in the mouse pancreas

机译:Establishment of human pluripotent stem cell-derived pancreatic beta-like cells in the mouse pancreas

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摘要

Type 1 diabetes is characterized by autoimmune destruction of beta cells located in pancreatic islets. However, tractable in vivo models of human pancreatic beta cells have been limited. Here, we generated xenogeneic human pancreatic beta-like cells in the mouse pancreas by orthotopic transplantation of stem cell-derived beta (SC-beta) cells into the pancreas of neonatal mice. The engrafted beta-like cells expressed beta 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 beta-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-beta cells into neonatal mice is an experimental platform that allows the generation of mice with human pancreatic beta-like cells in the endogenous niche.

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