title: Insulin-secreting cells from human eyelid-derived stem cells alleviate type I diabetes in immunocompetent mice.
abstract: 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.
authors: Department of Biotechnology, Seoul Women's University, Seoul, Korea.
authors: Hyun Mi
authors: HM
authors: Kang
authors: Jiyoung
authors: J
authors: Kim
authors: Seah
authors: S
authors: Park
authors: Jinyoung
authors: J
authors: Kim
authors: Haekwon
authors: H
authors: Kim
authors: Kyung Sik
authors: KS
authors: Kim
authors: Eun Jig
authors: EJ
authors: Lee
authors: Sung Ig
authors: SI
authors: Seo
authors: Sung Goo
authors: SG
authors: Kang
authors: Jong-Eun
authors: JE
authors: Lee
authors: Hyunjung
authors: H
authors: Lim
mesh_terms: 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
chemical_list: D007328:Insulin