Human amnion epithelial cells can be induced to differentiate into functional insulin-producing cells.
Pancreatic islet transplantation has demonstrated that long-term insulin independence may be achieved in patients suffering from diabetes mellitus type 1. However, limited availability of islet tissue means that new sources of insulin-producing cells that are responsive to glucose are required. Here, we show that human amnion epithelial cells (HAEC) can be induced to differentiate into functional insulin-producing cells in vitro. After induction of differentiation, HAEC expressed multiple pancreatic beta-cell genes, including insulin, pancreas duodenum homeobox-1, paired box gene 6, NK2 transcription factor-related locus 2, Islet 1, glucokinase, and glucose transporter-2, and released C-peptide in a glucose-regulated manner in response to other extracellular stimulations. The transplantation of induced HAEC into streptozotocin-induced diabetic C57 mice reversed hyperglycemia, restored body weight, and maintained euglycemia for 30 d. These findings indicated that HAEC may be a new source for cell replacement therapy in type 1 diabetes.
Hou
Yanan
Y
Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
Huang
Qin
Q
Liu
Tianjin
T
Guo
Lihe
L
D000650:Amnion / Q000378:metabolism* / Q000601:surgery / Q000637:transplantation; D000818:Animals; D002096:C-Peptide / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects*; D002478:Cells, Cultured; D016895:Culture Media, Serum-Free; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism / Q000601:surgery; D003922:Diabetes Mellitus, Type 1 / Q000628:therapy; D004847:Epithelial Cells / Q000378:metabolism* / Q000637:transplantation; D005947:Glucose / Q000378:metabolism / Q000494:pharmacology*; D006801:Humans; D006943:Hyperglycemia / Q000378:metabolism / Q000601:surgery / Q000628:therapy; D050417:Insulin-Secreting Cells / Q000378:metabolism* / Q000637:transplantation; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D011863:Radioimmunoassay; D013997:Time Factors
D002096:C-Peptide; D016895:Culture Media, Serum-Free; D005947:Glucose