Establishment of human pluripotent stem cell-derived pancreatic β-like cells in the mouse pancreas

Haiting Ma, Katherine J. Wert, Dmitry Shvartsman, Douglas A. Melton, Rudolf Jaenisch

Research output: Contribution to journalArticle

6 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)3924-3929
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume115
Issue number15
DOIs
StatePublished - Jan 1 2018
Externally publishedYes

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Pluripotent Stem Cells
Pancreas
Islets of Langerhans
Pancreas Transplantation
Endocrine Cells
Acinar Cells
Blood Circulation
Stem Cell Transplantation
Type 1 Diabetes Mellitus

Keywords

  • Beta cells
  • Diabetes
  • Human pluripotent stem cells
  • Humanized mice

ASJC Scopus subject areas

  • General

Cite this

Establishment of human pluripotent stem cell-derived pancreatic β-like cells in the mouse pancreas. / Ma, Haiting; Wert, Katherine J.; Shvartsman, Dmitry; Melton, Douglas A.; Jaenisch, Rudolf.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 115, No. 15, 01.01.2018, p. 3924-3929.

Research output: Contribution to journalArticle

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