Insulin‐Secreting Cells from Human Eyelid‐Derived Stem Cells Alleviate Type I Diabetes in Immunocompetent Mice

• Published in: Stem cells (Dayton, Ohio) Vol. 27; no. 8; pp. 1999 - 2008
• Main Authors: Kang, Hyun Mi, Kim, Jiyoung, Park, Seah, Kim, Jinyoung, Kim, Haekwon, Kim, Kyung Sik, Lee, Eun Jig, Seo, Sung Ig, Kang, Sung Goo, Lee, Jong‐Eun, Lim, Hyunjung
• Format: Journal Article
• Language: English
• Published: Hoboken Wiley Subscription Services, Inc., A Wiley Company 01.08.2009
• Subjects: 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; Human eyelid adipose; Humans; Immunocompetent; Insulin; 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; Stem Cell Transplantation - methods; Stem Cells - cytology; Stem Cells - physiology; Type I diabetes; Young Adult; β cell
• ISSN: 1066-5099; 1549-4918
• DOI: 10.1002/stem.127

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. STEM CELLS 2009;27:1999–2008