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比较脐血和外周血来源的内皮祖细胞的蛋白质组学分析及其在细胞治疗中的应用。

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

机构信息

CHA Bio & Diostech Co., Ltd., 606-16 Yeoksam 1 dong, Gangnam gu, Seoul 135-907, Republic of Korea.

出版信息

Biomaterials. 2013 Feb;34(6):1669-85. doi: 10.1016/j.biomaterials.2012.11.017. Epub 2012 Dec 3.

Abstract

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.

摘要

缺血导致的组织损伤性血管病变是发病率和死亡率的主要原因。为了治疗这些疾病,已经将各种来源(如脐带或外周血)的内皮祖细胞(EPC)作为再生医学领域的焦点,因为它们具有增殖和血管生成活性。然而,不同细胞来源的 EPC 之间的基本分子水平差异很少得到研究。在这项研究中,我们建立了来源于脐带血和外周血的内皮祖细胞(CB-EPC 和 PB-EPC),并通过干细胞生物学技术和蛋白质组学分析相结合,研究了它们在细胞和分子水平上的基本差异。我们的结果表明,CB-EPC 中特异性上调的因子,如 STMIN1、CFL1、PARK7、NME1、GLO1、HSP27 和 PRDX2 等,可能是在缺血区域发挥功能的关键因素。我们还讨论了在缺血条件下诱导和维持持久血管的重要功能行为。结果表明,CB-EPC 在体外比 PB-EPC 具有更高的抗氧化和迁移能力。此外,CB-EPC 在下肢缺血疾病模型中比 PB-EPC 具有更高的治疗效果。STMIN1、CFL1、PARK7、NME1、GLO1、HSP27 和 PRDX2 的上调表达模式在体外和体内的几种条件下得到了证实,表明 CB-EPC 中这些分子的上调可能对缺血条件下的愈合机制至关重要,并且 CB-EPC 可能更适合诱导新血管生成。因此,这些结果可能有助于预测哪种细胞来源对基于细胞的病理条件治疗具有价值,并确定几种可能参与缺血治疗机制的候选分子。

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