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Comparative proteomic analysis of endothelial cells progenitor cells derived from cord blood- and peripheral blood for cell therapy

机译:脐血和外周血来源的内皮细胞祖细胞用于细胞治疗的比较蛋白质组学分析

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Vasculopathy due to ischemia in damaged tissues is a major cause of morbidity and mortality. To treat these conditions, endothelial progenitor cells (EPCs) from various sources, such as umbilical cord or peripheral blood, have been the focus of the regenerative medicine field due to their proliferative and vasculogenic activities. However, the fundamental, molecular-level differences between EPCs obtained from different cellular sources have rarely been studied. In this study, we established endothelial progenitor cells derived from cord blood- and peripheral blood (CB- and PB-EPCs) and investigated their fundamental differences at the cellular and molecular levels through a combination of stem cell biology techniques and proteomic analysis. Our results suggest that specifically up-regulated factors such as STMIN 1, CFL 1, PARK 7, NME 1, GLO 1, HSP 27 and PRDX 2 in CB-EPCs as key elements that could be functionally active in ischemic regions. We also discussed functional behaviors important for inducing and maintaining long-lasting blood vessels under ischemic conditions. As a result, CB-EPCs retained a higher anti-oxidant and migration ability than PB-EPCs in vitro. Furthermore, CB-EPCs retained a higher therapeutic efficacy than PB-EPCs in a hindlimb ischemic disease model. The up-regulated expression pattern of STMIN 1, CFL 1, PARK 7, NME 1, GLO 1, HSP 27 and PRDX 2 was confirmed under several conditions in vitro and in vivo, indicating that the up-regulation of these molecules in CB-EPCs may be critical to the mechanism of healing in ischemic conditions and that CB-EPCs may be more appropriate for inducing neo-vessels. Thus, these results may aid in predetermining which cell sources will be of value for cell-based therapies of pathological conditions and identify several candidate molecules that may be involved in the therapeutic mechanism for ischemia.
机译:受损组织中缺血引起的血管病变是发病和死亡的主要原因。为了治疗这些状况,由于其增殖和血管生成活性,来自各种来源的内皮祖细胞(EPC),例如脐带血或外周血,已经成为再生医学领域的重点。但是,很少研究从不同细胞来源获得的EPC之间基本的分子水平差异。在这项研究中,我们建立了脐带血和外周血(CB-和PB-EPC)衍生的内皮祖细胞,并通过结合干细胞生物学技术和蛋白质组学分析研究了它们在细胞和分子水平上的根本差异。我们的结果表明,CB-EPCs中特定上调的因子(例如STMIN 1,CFL 1,PARK 7,NME 1,GLO 1,HSP 27和PRDX 2)是可能在缺血区域发挥功能的关键元素。我们还讨论了在缺血条件下对诱导和维持长效血管至关重要的功能行为。结果,CB-EPC在体外比PB-EPC保留了更高的抗氧化和迁移能力。此外,在后肢缺血性疾病模型中,CB-EPC比PB-EPC保留更高的治疗功效。在体外和体内的几种条件下,证实了STMIN 1,CFL 1,PARK 7,NME 1,GLO 1,HSP 27和PRDX 2的表达上调,表明这些分子在CB- EPC对缺血性疾病的康复机制可能至关重要,而CB-EPC可能更适合诱导新血管。因此,这些结果可以帮助预先确定哪些细胞来源对于病理性疾病的基于细胞的治疗具有价值,并鉴定出可能参与局部缺血治疗机制的几种候选分子。

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