Human endometrial stem cells confer enhanced myocardial salvage and regeneration by paracrine mechanisms.

Human endometrial stem cells confer enhanced myocardial salvage and regeneration by paracrine mechanisms.
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人子宫内膜干细胞通过旁分泌机制增强心肌挽救和再生

DOI:
10.1111/jcmm.12100
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发表时间:
2013-10
影响因子:
5.3
通讯作者:
Wang JA
Wang JA
中科院分区:
医学2区
文献类型:
--
作者:
Jiang Z;Hu X;Yu H;Xu Y;Wang L;Chen H;Chen H;Wu R;Zhang Z;Xiang C;Webster KA;Wang JA

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人子宫内膜干细胞(EnSC)有可能成为治疗心力衰竭的“现成”临床试剂。在这里,使用免疫功能正常的大鼠模型心肌梗死(MI),我们提供的证据表明,功能的好处,EnSC移植主要是通过旁分泌效应,并可能完全。在冠状动脉结扎后30分钟,通过心肌内注射将人EnSC递送到大鼠中。EnSC治疗在28天时显著保留了梗死区的存活心肌并改善了心功能。尽管存活心肌和血管密度增加,但缺乏证据表明EnSC分化为任何心血管细胞类型。培养的人EnSC表达一种独特的细胞因子谱,其在体外增强内皮细胞的存活、增殖和功能。当注射到梗死周围区时,人EnSC激活AKT,ERK 1/2和STAT 3并抑制p38信号通路。EnSC治疗在体内减少细胞凋亡并促进细胞增殖和c-kit+细胞募集。EnSC的心肌保护和增强的梗死后再生主要由分泌的细胞因子赋予的旁分泌效应介导,所述细胞因子激活存活途径并募集内源性祖干细胞。脐带血为同种异体心肌再生医学提供了一个潜在的无限的生物活性“现成”EnSC来源。
Human endometrial stem cells (EnSCs) have the potential to be ‘off the shelf’ clinical reagents for the treatment of heart failure. Here, using an immunocompetent rat model of myocardial infarction (MI), we provide evidence that the functional benefits of EnSC transplantation are principally and possibly exclusively through a paracrine effect. Human EnSCs were delivered by intramyocardial injection into rats 30 min. after coronary ligation. EnSC therapy significantly preserved viable myocardium in the infarct zone and improved cardiac function at 28 days. Despite increased viable myocardium and vascular density, there was scant evidence of differentiation of EnSCs into any cardiovascular cell type. Cultured human EnSCs expressed a distinctive profile of cytokines that enhanced the survival, proliferation and function of endothelial cells in vitro. When injected into the peri-infarct zone, human EnSCs activated AKT, ERK1/2 and STAT3 and inhibited the p38 signalling pathway. EnSC therapy decreased apoptosis and promoted cell proliferation and c-kit+ cell recruitment in vivo. Myocardial protection and enhanced post-infarction regeneration by EnSCs is mediated primarily by paracrine effects conferred by secreted cytokines that activate survival pathways and recruit endogenous progenitor stem cells. Menstrual blood provides a potentially limitless source of biologically competent ‘off the shelf’ EnSCs for allogeneic myocardial regenerative medicine.
子宫内膜再生细胞:一种新型的干细胞群体。
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