Generation of insulin-producing cells from PDX-1 gene-modified human mesenchymal stem cells

被引:118
作者
Li, Yanhua
Zhang, Rui
Qiao, Haifa
Zhang, Heping
Wang, Yunfang
Yuan, Hongfeng
Liu, Qinbin
Liu, Daqing
Chen, Lin
Pei, Xuetao
机构
[1] Beijing Inst Transfus Med, Dept Stem Cells & Regenerat Med, Beijing 100850, Peoples R China
[2] Beijing Inst Pharmacol & Toxicol, Dept Neuropharmacol, Beijing, Peoples R China
关键词
D O I
10.1002/jcp.20897
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Islet cell replacement is considered as the optimal treatment for type I diabetes. However, the availability of human pancreatic islets for transplantation is limited. Here, we show that human bone marrow-derived mesenchymal stem cells (hMSCs) could be induced to differentiate into functional insulin-producing cells by introduction of the pancreatic duodenal homeobox-1 (PDX-1). Recombinant adenoviral vector was used to deliver PDX-1 gene into hMSCs. After being infected with Ad-PDX-1, hMSCs were successfully induced to differentiate into insulin-secreting cells. The differentiated PDX-1(+) hMSCs expressed multiple islet-cell genes including neurogenin3 (Ngn3), insulin, GK, Glut2, and glucagon, produced and released insulin/C-peptide in a weak glucose-regulated manner. After the differentiated PDX-1 hMSCs were transplanted into STZ-induced diabetic mice, euglycemia can be obtained within 2 weeks and maintained for at least 42 days. These findings validate the hMSCs model system as a potential basis for enrichment of human beta cells or their precursors, and a possible source for cell replacement therapy in diabetes.
引用
收藏
页码:36 / 44
页数:9
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