Influence of Human Allogenic Bone Marrow and Cord Blood-Derived Mesenchymal Stem Cell Secreting Trophic Factors on ATP (adenosine-5′-triphosphate)/ADP (adenosine-5'-diphosphate) Ratio and Insulin Secretory Function of Isolated Human Islets From Cadaveric Donor

Influence of Human Allogenic Bone Marrow and Cord Blood-Derived Mesenchymal Stem Cell Secreting Trophic Factors on ATP (adenosine-5′-triphosphate)/ADP (adenosine-5'-diphosphate) Ratio and Insulin Secretory Function of Isolated Human Islets From Cadaveric Donor
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DOI:
10.1016/j.transproceed.2009.06.193
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发表时间:
2009-11-01
影响因子:
0.9
通讯作者:
Kim, S. J.
Kim, S. J.
中科院分区:
医学4区
文献类型:
--
作者:
Park, K. S.;Kim, Y. S.;Kim, S. J.

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成功的胰岛移植(ITx)不仅取决于胰岛的数量,还取决于其质量,包括生存能力、代谢活性和功能。胰岛质量在分离后的培养过程中下降。为了克服这一障碍,我们建立了胰岛和间充质干细胞(MSCs)共培养的做法。这种共培养条件改善了体外ATP(腺苷-5′-三磷酸)/ADP(腺苷-5′-二磷酸)比值和胰岛素分泌功能。胰岛-间充质干细胞共培养中胰岛质量的提高可能是由间充质干细胞分泌活性物质引起的。通过酶联免疫吸附试验(ELISA),我们发现白细胞介素-6 (IL-6)、血管内皮生长因子- a (VEGF-A)、肝细胞生长因子(HGF)和转化生长因子- β (tgf - β)在msc培养培养基中显著增加,这些因子已被证明可以改善胰岛的存活、功能和血管生成/血运重建。这些结果表明,骨髓间充质干细胞分泌的营养分子提高了胰岛的质量,影响了胰岛细胞内ATP含量和胰岛素分泌功能。
Successful islet transplantation (ITx) is not only dependent on the number of islets, but also their quality, including viability, metabolic activity, and function. Islet quality decreases during cultivation after the isolation procedure. To overcome this obstacle, we established the practice of islet and mesenchymal stem cells (MSCs) coculture. This coculture condition improved the ATP (adenosine-5'-triphosphate)/ADP (adenosine-5'-diphosphate) ratio and insulin secretory function in vitro. It is believed that the enhancement of islet quality in islet-MSCs cocultures may be caused by the secretion of active agents by MSCs. Herein we have shown that interleukin-6 (IL-6), vascular endothelial growth factor-A (VEGF-A), hepatocyte growth factor (HGF), and transforming growth factor-beta (TGF-beta) were significantly increased as measured by enzyme-linked immunosorbent assay (ELISA) in MSCs-cultured medium, factors that have been shown to improve the survival, function, and angiogenesis/revascularization of islets. These results indicated that the quality of human islets was enhanced by trophic molecules secreted by MSCs, which influence the intracellular islet ATP content and insulin secretory function.