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Insulin-secreting cells from human eyelid-derived stem cells alleviate type I diabetes in immunocompetent mice

Authors
 HYUN MI KANG  ;  JIYOUNG KIM  ;  SEAH PARK  ;  JINYOUNG KIM  ;  HAEKWON KIM  ;  KYUNG SIK KIM  ;  EUN JIG LEE  ;  SUNG IG SEO  ;  SUNG GOO KANG  ;  JONG-EUN LEE  ;  HYUNJUNG LIM 
Citation
 STEM CELLS, Vol.27(8) : 1999-2008, 2009 
Journal Title
 STEM CELLS 
ISSN
 1066-5099 
Issue Date
2009
MeSH
Adipose Tissue/cytology* ; Adolescent ; Adult ; Aged ; Animals ; Cell Differentiation ; Cells, Cultured ; Child ; Diabetes Mellitus, Experimental/blood ; Diabetes Mellitus, Experimental/surgery ; Diabetes Mellitus, Type 1/blood ; Diabetes Mellitus, Type 1/surgery* ; Eyelids/cytology ; Humans ; Insulin/metabolism ; Insulin/secretion* ; Insulin-Secreting Cells/cytology* ; Insulin-Secreting Cells/drug effects ; Insulin-Secreting Cells/metabolism ; Insulin-Secreting Cells/transplantation* ; Mice ; Middle Aged ; Stem Cell Transplantation/methods ; Stem Cells/cytology* ; Stem Cells/physiology ; Young Adult
Keywords
Human eyelid adipose ; Stem cell ; Type I diabetes ; bcell ; Insulin ; Immunocompetent
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
Files in This Item:
T200903470.pdf Download
DOI
10.1002/stem.127
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Surgery (외과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
Yonsei Authors
Kim, Kyung Sik(김경식) ORCID logo https://orcid.org/0000-0001-9498-284X
Lee, Eun Jig(이은직) ORCID logo https://orcid.org/0000-0002-9876-8370
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/105061
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