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首页> 外文期刊>Stem cells international >IGF-1-Overexpressing Mesenchymal Stem/Stromal Cells Promote Immunomodulatory and Proregenerative Effects in Chronic Experimental Chagas Disease
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IGF-1-Overexpressing Mesenchymal Stem/Stromal Cells Promote Immunomodulatory and Proregenerative Effects in Chronic Experimental Chagas Disease

机译：IGF-1-过度抑制间充质茎/基质细胞促进慢性实验性Chagas疾病中的免疫调节和预应力

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摘要

Mesenchymal stem/stromal cells (MSCs) have been investigated for the treatment of diseases that affect the cardiovascular system, including Chagas disease. MSCs are able to promote their beneficial actions through the secretion of proregenerative and immunomodulatory factors, including insulin-like growth factor-1 (IGF-1), which has proregenerative actions in the heart and skeletal muscle. Here, we evaluated the therapeutic potential of IGF-1-overexpressing MSCs (MSC_IGF-1) in a mouse model of chronic Chagas disease. C57BL/6 mice were infected with Colombian strain Trypanosoma cruzi and treated with MSCs, MSC_IGF-1, or vehicle (saline) six months after infection. RT-qPCR analysis confirmed the presence of transplanted cells in both the heart and skeletal muscle tissues. Transplantation of either MSCs or MSC IGF-1 reduced the number of inflammatory cells in the heart when compared to saline controls. Moreover, treatment with MSCs or MSC_IGF-1 significantly reduced TNF-alpha, but only MSC treatment reduced IFN-gamma production compared to the saline group. Skeletal muscle sections of both MSC- and MSC_IGF-1-treated mice showed a reduction in fibrosis compared to saline controls. Importantly, the myofiber area was reduced in T. cruzi-infected mice, and this was recovered after treatment with MSC_IGF-1. Gene expression analysis in the skeletal muscle showed a higher expression of pro- and anti-inflammatory molecules in MSC_IGF-i-treated mice compared to MSCs alone, which significantly reduced the expression of TNF-alpha and IL-1 beta. In conclusion, our results indicate the therapeutic potential of MSC_IGF-1, with combined immunomodulatory and proregenerative actions to the cardiac and skeletal muscles.
机译：已经研究了间充质茎/基质细胞（MSCs）用于治疗影响心血管系统的疾病，包括钩状病。 MSCs能够通过分泌预应性和免疫调节因子，包括胰岛素样生长因子-1（IGF-1）来促进其有益的作用，其在心脏和骨骼肌中具有预应性作用。在这里，我们在慢性噬菌氏病的小鼠模型中评估了IGF-1-过表达MSCs（MSC_IGF-1）的治疗潜力。 C57BL / 6小鼠用哥伦比亚菌株胰蛋白酶瘤Cruzi感染，并在感染后六个月用MSC，MSC_IGF-1或载体（盐水）处理。 RT-QPCR分析证实了心脏和骨骼肌组织中的移植细胞的存在。与盐水对照相比，MSCs或MSC IGF-1的移植减少了心脏中炎性细胞的数量。此外，用MSCs或MSC_IGF-1治疗显着降低TNF-α，但仅与盐水组相比，仅MSC处理减少了IFN-Gamma生产。与盐水对照相比，MSC和MSC_IGF-1治疗小鼠的骨骼肌部分表现出纤维化的降低。重要的是，在用MSC_IGF-1处理后，肌纤维区域降低了克鲁齐感染的小鼠。与单独的MSCs相比，骨骼肌中的基因表达分析表达MSC_IGF-I处理的小鼠中的促炎和抗炎分子的表达，这显着降低了TNF-α和IL-1β的表达。总之，我们的结果表明MSC_IGF-1的治疗潜力，具有对心脏和骨骼肌的综合免疫调节和预处理作用。

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