In vitro reprogramming of rat bone marrow-derived mesenchymal stem cells into insulin-producing cells by genetically manipulating negative and positive regulators

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• 作者：Hong-Tu Li^a ; ^d ; ¹ ; Fang-Xu Jiang^b ; ¹ ; ^{fangxu.jiang@uwa.edu.au} ; Ping Shi^c ; ¹ ; Tao Zhang^a ; Xiao-Yu Liu^a ; Xue-Wen Lin^a ; Xi-Ning Pang^a ; ^{pxining@yahoo.com}
• 关键词：bmMSCs ; bone marrow-derived mesenchymal stem cells ; Rest/Nrsf ; repressor element-1 silencing transcription factor/neuronal restrictive silencing factor ; Shh ; sonic hedgehog ; Pdx1 ; pancreas and duodenal transcription factor 1 ; GFP ; green fluorescent protei
• 刊名：Biochemical and Biophysical Research Communications
• 出版年：2012
• 出版时间：20 April, 2012
• 年：2012
• 卷：420
• 期：4
• 页码：793-798
• 全文大小：817 K

文摘

Islet cell replacement therapy represents the most promising approach for the cure of type 1 diabetes if autoimmunity to ¦Â cells is under control. However, this potential is limited by a shortage of pancreas donors. To address the donor shortage problem, we determined whether bone marrow-derived mesenchymal stem cells (bmMSCs) can be directly reprogrammed to islet lineages by simultaneously forced suppression and over-expression of key regulator genes that play critical roles during pancreas development. Here, we report that rat bmMSCs were converted in vitro into insulin-producing cells by suppressing two-repressor genes repressor element-1 silencing transcription factor/neuronal restrictive silencing factor (Rest/Nrsf) and sonic hedgehog (Shh) and by over-expressing pancreas and duodenal transcription factor 1 (Pdx1). The reprogrammed bmMSCs expressed both genes and proteins specific for islet cells. These converted cells were capable of releasing insulin in a glucose-responsive manner. Our study suggests that bmMSCs may ultimately be reprogrammed to functional insulin-secreting cells.