Accelerated Maturation of Human Stem Cell-Derived Pancreatic Progenitor Cells into Insulin-Secreting Cells in Immunodeficient Rats Relative to Mice

Stem Cell Reports. 2015 Dec 8;5(6):1081-1096. doi: 10.1016/j.stemcr.2015.10.013. Epub 2015 Nov 19.


Pluripotent human embryonic stem cells (hESCs) are a potential source of transplantable cells for treating patients with diabetes. To investigate the impact of the host recipient on hESC-derived pancreatic progenitor cell maturation, cells were transplanted into immunodeficient SCID-beige mice or nude rats. Following the transplant, basal human C-peptide levels were consistently higher in mice compared with rats, but only rats showed robust meal- and glucose-responsive human C-peptide secretion by 19-21 weeks. Grafts from rats contained a higher proportion of insulin:glucagon immunoreactivity, fewer exocrine cells, and improved expression of mature β cell markers compared with mice. Moreover, ECM-related genes were enriched, the collagen network was denser, and blood vessels were more intricately integrated into the engrafted endocrine tissue in rats relative to mice. Overall, hESC-derived pancreatic progenitor cells matured faster in nude rats compared with SCID-beige mice, indicating that the host recipient can greatly influence the fate of immature pancreatic progenitor cells post-transplantation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • C-Peptide / analysis
  • Cell Differentiation
  • Cell Line
  • Cells, Cultured
  • Embryonic Stem Cells / cytology*
  • Female
  • Humans
  • Insulin-Secreting Cells / cytology*
  • Male
  • Mice
  • Mice, SCID
  • Middle Aged
  • Pancreas / cytology*
  • Rats
  • Rats, Nude
  • Species Specificity
  • Stem Cell Transplantation*


  • C-Peptide