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首页> 外文期刊>Journal of Autoimmunity >Autologous bone marrow-derived rat mesenchymal stem cells promote PDX-1 and insulin expression in the islets, alter T cell cytokine pattern and preserve regulatory T cells in the periphery and induce sustained normoglycemia.
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Autologous bone marrow-derived rat mesenchymal stem cells promote PDX-1 and insulin expression in the islets, alter T cell cytokine pattern and preserve regulatory T cells in the periphery and induce sustained normoglycemia.

机译:自体骨髓源性大鼠间充质干细胞可促进胰岛中PDX-1和胰岛素的表达,改变T细胞的细胞因子模式,并在外周保留调节性T细胞,并诱导持续的正常血糖。

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摘要

Cell-based therapies offer considerable promise for prevention or cure of diabetes. We explored the potential of autologous, self-renewing, mesenchymal stem cells (MSC) as a clinically-applicable approach to promote glucose homeostasis. In vitro-expanded syngeneic bone marrow-derived MSC were administered following or prior to diabetes induction into a rat model of streptozotocin-induced beta cell injury. MSC were CD45(-)/CD44(+)/CD54(+)/CD90(+)/CD106(+). MSC spontaneously secreted IL-6, HGF, TGF-beta1 and expressed high levels of SDF-1 and low levels of VEGF, IL-1beta and PGE(2), but no EGF, insulin or glucagon. MSC homed to the pancreas and this therapy allowed for enhanced insulin secretion and sustained normoglycemia. Interestingly, immunohistochemistry demonstrated that, the islets from MSC-treated rats expressed high levels of PDX-1 and that these cells were also positive for insulin staining. In addition, peripheral T cells from MSC-treated rats exhibited a shift toward IL-10/IL-13 production and higher frequencies of CD4(+)/CD8(+) Foxp3(+) T cells compared to the PBS-treated rats. These data suggest that the bioactive factors secreted by MSC establish a tissue microenvironment that supports beta cell activation/survival in the pancreas. In addition, because of anti-inflammatory and immunoregulatory effects of MSC on T cells, this work can lead to clinical trial of autologous MSC to prevent/cure type-1 diabetes.
机译:基于细胞的疗法为预防或治愈糖尿病提供了可观的前景。我们探讨了自体,自我更新,间充质干细胞(MSC)作为促进葡萄糖体内稳态的临床适用方法的潜力。在糖尿病诱导后或之前,将体外扩增的同基因骨髓来源的MSC施用到链脲佐菌素诱导的β细胞损伤的大鼠模型中。 MSC是CD45(-)/ CD44(+)/ CD54(+)/ CD90(+)/ CD106(+)。 MSC自发分泌IL-6,HGF,TGF-beta1,并表达高水平的SDF-1和低水平的VEGF,IL-1beta和PGE(2),但没有EGF,胰岛素或胰高血糖素。 MSC归巢于胰腺,该疗法可增强胰岛素分泌和持续的正常血糖。有趣的是,免疫组织化学表明,经MSC治疗的大鼠的胰岛表达高水平的PDX-1,并且这些细胞的胰岛素染色也呈阳性。此外,与PBS处理的大鼠相比,MSC处理的大鼠的外周T细胞表现出向IL-10 / IL-13产生的转变,并且CD4(+)/ CD8(+)Foxp3(+)T细胞的频率更高。这些数据表明,由MSC分泌的生物活性因子建立了支持胰腺β细胞活化/存活的组织微环境。此外,由于MSC对T细胞的抗炎和免疫调节作用,这项工作可导致自体MSC预防/治愈1型糖尿病的临床试验。

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