title: Enhanced differentiation of human adipose tissue-derived stromal cells into insulin-producing cells with glucagon-like peptide-1.
abstract: Type 1 diabetes mellitus (T1DM) is mainly caused by reduction of the endogenous insulin secretion due to autoimmune destruction of pancreatic β cells, and a promising therapeutic approach for T1DM is pancreas and islet cell replacement. The major obstacle is the limited source of insulin-producing cells. Here, we report an efficient approach to induce human adipose-derived stromal cells (hADSCs) to differentiate into insulin-producing cells, with glucagon-like peptide-1 (GLP-1). hADSCs were successfully isolated from the adipose tissue, with adipogenic and osteogenic differentiation potency. Islet-like cell clusters formed in the culture, which was enhanced with the treatment of GLP-1. Reverse transcription polymerase chain reaction analysis showed the expression of the pancreas-related genes in the differentiated cells, such as pdx-1, ngn3, insulin, glucagon, somatostatin, glucokinase n and glut2. Immunocytochemical analysis showed that the induced cells co-expressed insulin, C-peptide and PDX-1. The GLP-1 receptor was present in the differentiated cells. In addition, flow cytometry analysis and ELISA showed that, in the presence of GLP-1, the percentage of insulin-producing cells was increased from 5.9% to 28.0% and the release of insulin increased from 9.53±0.7 pmol/106 cells to 15.86±1.3 pmol/106 cells. Insulin was released in response to glucose stimulation in a manner comparable to that of adult human islets. These results indicated that hADSCs isolated from adipose tissues can be induced to differentiate into insulin-producing cells, which is further enhanced with the treatment of GLP-1. These findings confirm that the differentiation of hADSCs to insulin-producing cells is indeed possible and indicate that the differentiated insulin-producing cells can be used as a potential source for transplantation into patients with T1DM.
authors.affiliation: College of Pharmacy, Jilin University, Changchun, China.
authors.forename: A-H
authors.initials: AH
authors.lastname: Wei
authors.forename: W-J
authors.initials: WJ
authors.lastname: Wang
authors.forename: X-P
authors.initials: XP
authors.lastname: Mu
authors.forename: H-M
authors.initials: HM
authors.lastname: Li
authors.forename: W-Q
authors.initials: WQ
authors.lastname: Yan
mesh_terms: D000273:Adipose Tissue / Q000166:cytology* / Q000378:metabolism*; D000328:Adult; D000943:Antigens, Differentiation / Q000096:biosynthesis; D002454:Cell Differentiation / Q000187:drug effects*; D002478:Cells, Cultured; D003922:Diabetes Mellitus, Type 1 / Q000378:metabolism / Q000628:therapy; D005260:Female; D052216:Glucagon-Like Peptide 1 / Q000494:pharmacology*; D006801:Humans; D054795:Incretins / Q000494:pharmacology*; D050417:Insulin-Secreting Cells / Q000637:transplantation; D008297:Male; D017154:Stromal Cells / Q000166:cytology / Q000378:metabolism
chemical_list: D000943:Antigens, Differentiation; D054795:Incretins; D052216:Glucagon-Like Peptide 1