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Generation of Insulin-Producing Cells from Bone Marrow Mesenchymal Stem Cells with Modified Expression of PDX1 and NKX6.1

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机构: [1]Stem Cell Engineering Research Center, School of Medical, Anhui University of Science & Technology, Huainan 232001, P.R. China [2]Nankai Hospital, Nankai Clinical School, Tianjin Medical University, Tianjin 300100, P.R. China [3]Clinical Laboratory, Second Affiliated Hospital, Guangzhou University of Traditional Chinese Medicine (Guangdong Provincial Hospital of TCM), Guangzhou 510120, P.R. China [4]Department of Microbiology and Immunology, School of Medical, Jinan University, Guangzhou 510632, P.R. China [5]Clinical Laboratory, Liuzhou worker’s Hospital, Guangxi 545005, P.R. China
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关键词: Pancreatic and duodenal homeobox factor 1 Adeno virus vector Insulin-producing cells Gene-modification

摘要:
This study was designed to efficiently induce the differentiation of the bone marrow mesenchymal stem cells (BMSCs) into insulin-producing islet cells by modifying the expression of pancreatic and duodenal homeobox factor 1 (PDX1) and NKX6 transcription factor related 1 (NKX6.1). Bone marrow mesenchymal stem cells were infected by the recombinant adeno viruses carrying Pdx1 and Nkx6.1 genes for differentiation and the differentiated cells were transplanted into the subrenal capsule of diabetic mice, then the secretion of insulin and C-peptide were examined. The effects of the differentiated cells were also investigated through measuring the blood glucose levels. The BMSCs induced by recombinant adeno virus of pAdxsi-CMV-PDX1/CMV-NKX6.1 and several cytokines showed positive dithizone staining and significant expression of insulin and glucose transporter-2. Stimulation with different levels of glucose caused different insulin secretion levels at 1240.4 +/- 109.3 and 3539.8 +/- 245.1 mU/L with 5.5 and 25 mmol/L treatments, respectively. More importantly, the transplantation of induced cells recovered the serum glucose in Streptozotocin mice to normal levels. Coexpression of exogenous PDX-1 and NKX6.1 efficiently induced the differentiation of BMSCs into insulin-producing cells, which restored the blood glucose levels in STZ-induced diabetic mice.

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出版当年[2013]版:
大类 | 4 区 化学
小类 | 4 区 化学综合
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出版当年[2012]版:
Q4 CHEMISTRY, MULTIDISCIPLINARY
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第一作者机构: [1]Stem Cell Engineering Research Center, School of Medical, Anhui University of Science & Technology, Huainan 232001, P.R. China [2]Nankai Hospital, Nankai Clinical School, Tianjin Medical University, Tianjin 300100, P.R. China
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