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Decreased immunomodulatory and secretory capability of aging human umbilical cord mesenchymal stem cells in vitro

机译:在体外减少衰老人脐带间充质干细胞的免疫调节和分泌能力

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Mesenchymal stem cell therapy has drawn much attention as a promising therapeutic option for the treatment of different diseases. Due to insufficient cell population derived from freshly isolated tissues, in vitro propagation is required prior to clinical use. However, reduced cell viability of aging mesenchymal stem cell (MSCs) with repeated propagations has yet not be fully investigated, especially for the biological characteristics of immunoregulatory ability and paracrine factors. In this study, we compared the biological properties of human umbilical cord-MSCs (hUC-MSCs) at different passages, especially for immunomodulatory ability and secretions. Our results showed that hUC-MSCs at early passage (P2) and late passage (P8) exhibited similar morphology and surface marker expression, but hUC-MSCs at P8 displayed reduced proliferation and differentiation potential, immunoregulatory and secretory ability. In particular, hUC-MSCs at P2 and P5 could significantly suppress the population of proinflammatory Th1 and Th17 cell subsets and upregulate Treg cells, but not with hUC-MSCs at P8. For paracrine mechanism, higher level of secretions such as growth factors, cell adhesions, anti-inflammatory factors of hUC-MSCs were observed at P2 and P5 compared to that at P8. Therefore, it is essential to verify and validate the biological characteristics of hUC-MSCs that possess a good vitality before they are released for clinical use. Altogether, this study provides a rationale and two important parameters for how to select appropriate passage and vitality of MSCs for cell therapy. (C) 2020 Elsevier Inc. All rights reserved.
机译:间充质干细胞疗法吸引了很多关注,作为治疗不同疾病的有希望的治疗选择。由于从新鲜分离的组织中衍生的细胞群体不足,在临床使用之前需要体外繁殖。然而,尚未得到完全研究衰老间充质干细胞(MSCs)的老化间充质干细胞(MSC)的细胞活力,特别是对于免疫调节能力和旁静脉因子的生物学特征。在这项研究中,我们将人脐带-MSCs(HUC-MSCs)的生物学特性与不同通道进行了比较,特别是对于免疫调节能力和分泌物。我们的研究结果表明,早期通道(P2)和晚期通道(P8)的HUC-MSCs表现出类似的形态和表面标志物表达,但P8的HUC-MSC显示出降低的增殖和分化势,免疫监测和分泌能力。特别地,P2和P5的HUC-MSCs可以显着抑制促炎致炎动α和Th17细胞亚群的群体,并在P8处用HUC-MSCs进行上调。对于旁静脉机制,与P2和P5以P8相比,在P2和P5中观察到较高水平的分泌物,例如生长因子,细胞粘连,HUC-MSCs的抗炎因子。因此,必须验证和验证HUC-MSCs的生物学特性,在释放临床用途之前具有良好的活力。完全,本研究提供了基本原理和两个重要参数,了解如何为细胞疗法选择适当的MSCs和活力。 (c)2020 Elsevier Inc.保留所有权利。

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