TY - JOUR
T1 - Differential Function and Maturation of Human Stem Cell-Derived Islets after Transplantation
AU - Maxwell, Kristina G.
AU - Kim, Michelle H.
AU - Gale, Sarah E.
AU - Millman, Jeffrey R.
N1 - Publisher Copyright:
© 2022 The Author(s).
PY - 2022/3
Y1 - 2022/3
N2 - 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.
AB - 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.
KW - cell transplantation
KW - diabetes mellitus
KW - insulin-secreting cells
KW - stem cells
KW - tissue-based therapy
UR - http://www.scopus.com/inward/record.url?scp=85128159980&partnerID=8YFLogxK
U2 - 10.1093/stcltm/szab013
DO - 10.1093/stcltm/szab013
M3 - Article
C2 - 35294547
AN - SCOPUS:85128159980
SN - 2157-6564
VL - 11
SP - 322
EP - 331
JO - Stem Cells Translational Medicine
JF - Stem Cells Translational Medicine
IS - 3
ER -