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大网膜来源的基质细胞通过强大的旁分泌机制改善猪梗死心脏的心肌再生。

Omentum-derived stromal cells improve myocardial regeneration in pig post-infarcted heart through a potent paracrine mechanism.

机构信息

Medestea Research and Production Laboratories, Consorzio Carso, 70010 Valenzano, Bari, Italy.

出版信息

Exp Cell Res. 2010 Jul 1;316(11):1804-15. doi: 10.1016/j.yexcr.2010.02.009. Epub 2010 Feb 12.

DOI:10.1016/j.yexcr.2010.02.009
PMID:20156437
Abstract

Cell-based therapy could be a valid option to treat myocardial infarct (MI). Adipose-derived stromal cells (ADStCs) have demonstrated tissue regenerative potential including cardiomyogenesis. Omentum is an extremely rich source of visceral fat and its accumulation seems to correlate with cardiovascular diseases. We investigated the capacity of human fat Omentum-derived StCs (FOStCs) to affect heart function upon acute infarct in pigs induced by permanent ligation of the anterior interventricular artery (IVA). We demonstrated for the first time that the local injection of 50x10(6) of FOStCs ameliorates the functional parameters of post-infarct heart. Most importantly, histology of FOStCs treated hearts demonstrated a substantial improvement of cardiomyogenesis. In culture, FOStCs produced an impressive number and amount of angiogenic factors and cytokines. Moreover, the conditioned medium of FOStCs (FOStCs-CM) stimulates in vitro cardiac endothelial cells (ECs) proliferation and vascular morphogenesis and inhibits monocytes, EC activation and cardiomyocyte apoptosis. Since FOStCs in vivo did not trans-differentiate into cardiomyocyte-like cells, we conclude that FOStCs efficacy was presumably mediated by a potent paracrine mechanism involving molecules that concomitantly improved angiogenesis, reduced inflammation and prevented cardiomyocytes death. Our results highlight for the first time the important role that human FOStCs may have in cardiac regeneration.

摘要

基于细胞的疗法可能是治疗心肌梗死(MI)的有效选择。脂肪来源的基质细胞(ADSCs)具有组织再生潜力,包括心肌生成。大网膜是内脏脂肪的极其丰富来源,其积累似乎与心血管疾病相关。我们研究了人脂肪大网膜来源的基质细胞(FOStCs)在通过永久性结扎前降支动脉(IVA)诱导的猪急性梗死时对心脏功能的影响。我们首次证明,局部注射 50x10(6)个 FOStCs 可改善梗死心脏的功能参数。最重要的是,FOStCs 治疗心脏的组织学显示出心肌生成的实质性改善。在培养中,FOStCs 产生了大量的血管生成因子和细胞因子。此外,FOStCs 的条件培养基(FOStCs-CM)刺激体外心脏内皮细胞(ECs)增殖和血管形态发生,并抑制单核细胞、EC 激活和心肌细胞凋亡。由于体内的 FOStCs 没有转分化为心肌样细胞,我们得出结论,FOStCs 的疗效可能是通过一种强大的旁分泌机制介导的,该机制涉及同时改善血管生成、减少炎症和防止心肌细胞死亡的分子。我们的结果首次强调了人 FOStCs 在心脏再生中可能具有的重要作用。

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