Insulin-secreting cells from human eyelid-derived stem cells alleviate type I diabetes in immunocompetent mice.
Various attempts have been made to develop stem cell-based therapy to alleviate type I diabetes using animal models. However, it has been a question whether human insulin produced from explanted cells is solely responsible for the normoglycemia of diabetic animals. In this study, we isolated neural crest-like stem cells from the human eyelid fat and examined their therapeutic potentials for diabetes. The human eyelid adipose-derived stem cells (HEACs) displayed characteristics of neural crest cells. Using a two-step culture condition combined with nicotinamide, activin, and/or GLP-1, we differentiated HEACs into insulin-secreting cells and examined in vivo effects of differentiated cells by transplantation experiments. Following differentiation in vitro, HEACs released insulin and c-peptide in a glucose-dependent manner. Upon their transplantation under kidney capsules of streptozotocin-treated immunocompetent mice, we observed normalization of hyperglycemia in 10 of 20 recipient mice until sacrifice after 2 months. Only the human, but not the mouse, insulin and c-peptide were detected in the blood of recipient mice. Removal of the kidneys transplanted with HEACs resulted in a sharp increase of blood glucose level. Removed kidney tissues showed distinct expression of various human genes including insulin, and colocalization of the human insulin and the human nuclear protein in many cells. However, they showed diminished or null expression of some immune-related genes. In conclusion, human insulin alone produced from eyelid-derived stem cells following differentiation into insulin-secreting cells and transplantation could normalize type I diabetes in mice.
Kang
Hyun Mi
HM
Department of Biotechnology, Seoul Women's University, Seoul, Korea.
Kim
Jiyoung
J
Park
Seah
S
Kim
Jinyoung
J
Kim
Haekwon
H
Kim
Kyung Sik
KS
Lee
Eun Jig
EJ
Seo
Sung Ig
SI
Kang
Sung Goo
SG
Lee
Jong-Eun
JE
Lim
Hyunjung
H
D000273:Adipose Tissue / Q000166:cytology*; D000293:Adolescent; D000328:Adult; D000368:Aged; D000818:Animals; D002454:Cell Differentiation; D002478:Cells, Cultured; D002648:Child; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000601:surgery; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000601:surgery*; D005143:Eyelids / Q000166:cytology; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism / Q000637:transplantation*; D051379:Mice; D008875:Middle Aged; D033581:Stem Cell Transplantation / Q000379:methods; D013234:Stem Cells / Q000166:cytology* / Q000502:physiology; D055815:Young Adult
D007328:Insulin