Exp Clin Endocrinol Diabetes 2012; 120(01): 28-34
DOI: 10.1055/s-0031-1280807
Article
© Georg Thieme Verlag KG Stuttgart · New York

Enhanced Differentiation of Human Adipose Tissue-derived Stromal Cells into Insulin-producing Cells with Glucagon-like Peptide-1

A.-H. Wei
1   College of Pharmacy, Jilin University, Changchun, China
,
W.-J. Wang
1   College of Pharmacy, Jilin University, Changchun, China
,
X.-P. Mu
2   China-Japan Union Hospital of Jilin University, Changchun, China
,
H.-M. Li
3   Clinical Laboratory, The Second Affiliated Hospital of Jilin University, Changchun, China
,
W.-Q. Yan
1   College of Pharmacy, Jilin University, Changchun, China
› Author Affiliations
Further Information

Publication History

received 18 March 2011
first decision 16 May 2011

accepted 03 June 2011

Publication Date:
13 September 2011 (online)

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.

 
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