Differential Function and Maturation of Human Stem Cell-Derived Islets After Transplantation

Kristina G. Maxwell, Michelle H. Kim, Sarah E. Gale, Jeffrey R. Millman

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

Insulin-producing stem cell-derived islets (SC-islets) provide a virtually unlimited cell source for diabetes cell replacement therapy. While SC-islets are less functional when first differentiated in vitro compared to isolated cadaveric islets, transplantation into mice has been shown to increase their maturation. To understand the effects of transplantation on maturation and function of SC-islets, we examined the effects of cell dose, transplantation strategy, and diabetic state in immunocompromised mice. Transplantation of 2 and 5, but not 0.75 million SC-islet cells underneath the kidney capsule successfully reversed diabetes in mice with pre-existing diabetes. SQ and intramuscular injections failed to reverse diabetes at all doses and had undetectable expression of maturation markers, such as MAFA and FAM159B. Furthermore, SC-islets had similar function and maturation marker expression regardless of diabetic state. Our results illustrate that transplantation parameters are linked to SC-islet function and maturation, providing ideal mouse models for preclinical diabetes SC therapy research.

Original languageEnglish
Pages (from-to)322-331
Number of pages10
JournalStem Cells Translational Medicine
Volume11
Issue number3
DOIs
StatePublished - Mar 31 2022

Keywords

  • cell transplantation
  • diabetes mellitus
  • insulin-secreting cells
  • stem cells
  • tissue-based therapy

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