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Insulin-Producing Cells Differentiated from Human Bone Marrow Mesenchymal Stem Cells In Vitro Ameliorate Streptozotocin-Induced Diabetic Hyperglycemia  期刊论文  

  • 编号:
    c6493408-ac35-4e3c-ba13-9b11c13cc345
  • 作者:
    Xin, Ying(辛颖)#[1,3]Jiang, Xin(姜新)[2]Wang, Yishu[1];Su, Xuejin[1];Sun, Meiyu[1];Zhang, Lihong[1];Tan, Yi[3];Wintergerst, Kupper A.[3];Li, Yan*[4]Li, Yulin(李玉林)*[1]
  • 语种:
    英文
  • 期刊:
    PLOS ONE ISSN:1932-6203 2016 年 11 卷 1 期 ; JAN 12
  • 收录:
  • 摘要:

    Background
    The two major obstacles in the successful transplantation of islets for diabetes treatment are inadequate supply of insulin-producing tissue and immune rejection. Induction of the differentiation of human bone marrow-derived mesenchymal stem cells (hMSCs) into insulinproducing cells (IPCs) for autologous transplantation may alleviate those limitations.
    Methods
    hMSCs were isolated and induced to differentiate into IPCs through a three-stage differentiation protocol in a defined media with high glucose, nicotinamide, and exendin-4. The physiological characteristics and functions of IPCs were then evaluated. Next, about 3 x 10(6) differentiated cells were transplanted into the renal sub-capsular space of streptozotocin (STZ)-induced diabetic nude mice. Graft survival and function were assessed by immunohistochemistry, TUNEL staining and measurements of blood glucose levels in the mice.
    Results
    The differentiated IPCs were characterized by Dithizone (DTZ) positive staining, expression of pancreatic beta-cell markers, and human insulin secretion in response to glucose stimulation. Moreover, 43% of the IPCs showed L-type Ca2+ channel activity and similar changes in intracellular Ca2+ in response to glucose stimulation as that seen in pancreatic beta-cells in the process of glucose-stimulated insulin secretion. Transplantation of functional IPCs into the renal subcapsular space of STZ-induced diabetic nude mice ameliorated the hypergly-cemia. Immunofluorescence staining revealed that transplanted IPCs sustainably expressed insulin, c-peptide, and PDX-1 without apparent apoptosis in vivo.
    Conclusions
    IPCs derived from hMSCs in vitro can ameliorate STZ-induced diabetic hyperglycemia, which indicates that these hMSCs may be a promising approach to overcome the limitations of islet transplantation.

  • 推荐引用方式
    GB/T 7714:
    Xin Ying,Jiang Xin,Wang Yishu, et al. Insulin-Producing Cells Differentiated from Human Bone Marrow Mesenchymal Stem Cells In Vitro Ameliorate Streptozotocin-Induced Diabetic Hyperglycemia [J].PLOS ONE,2016,11(1).
  • APA:
    Xin Ying,Jiang Xin,Wang Yishu,Su Xuejin,&Li Yulin.(2016).Insulin-Producing Cells Differentiated from Human Bone Marrow Mesenchymal Stem Cells In Vitro Ameliorate Streptozotocin-Induced Diabetic Hyperglycemia .PLOS ONE,11(1).
  • MLA:
    Xin Ying, et al. "Insulin-Producing Cells Differentiated from Human Bone Marrow Mesenchymal Stem Cells In Vitro Ameliorate Streptozotocin-Induced Diabetic Hyperglycemia" .PLOS ONE 11,1(2016).
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