Differentiation, Metabolism, and Cardioprotective Secretory Functions of Human Cardiac Stromal Cells from Ischemic and Endocarditis Patients.

Stem cells and development Pub Date : 2024-09-01 Epub Date: 2024-07-16 DOI:10.1089/scd.2024.0103
Helen Nguyen, Chuan-Chih Hsu, Annette Meeson, Rachel Oldershaw, Gavin Richardson, Andreas Czosseck, David J Lundy
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Abstract

This study investigates the characteristics of cardiac mesenchymal stem cell-like cells (CMSCLCs) isolated from the right atrial appendage of human donors with ischemia and a young patient with endocarditis (NE-CMSCLCs). Typical CMSCLCs from ischemic heart patients were derived from coronary artery bypass grafting procedures and compared against bone marrow mesenchymal stromal cells (BM-MSCs). NE-CMSCLCs had a normal immunophenotype, but exhibited enhanced osteogenic differentiation potential, rapid proliferation, reduced senescence, reduced glycolysis, and lower reactive oxygen species generation after oxidative stress compared with typical ischemic CMSCLCs. These differences suggest a unique functional status of NE-CMSCLCs, influenced by the donor health condition. Despite large variances in their paracrine secretome, NE-CMSCLCs retained therapeutic potential, as indicated by their ability to protect hypoxia/reoxygenation-injured human cardiomyocytes, albeit less effectively than typical CMSCLCs. This research describes a unique cell phenotype and underscores the importance of donor health status in the therapeutic efficacy of autologous cardiac cell therapy.

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来自缺血和心内膜炎患者的人类心脏基质细胞的分化、代谢和心脏保护分泌功能。
本研究调查了从缺血的人体捐献者和一名年轻的心内膜炎患者的右心房阑尾分离出来的心脏间充质干细胞样细胞(CMSCLCs)(NE-CMSCLCs)的特征。缺血性心脏病患者的典型 CMSCLCs 来自冠状动脉旁路移植手术,并与骨髓间充质基质细胞(BM-MSCs)进行了比较。NE-CMSCLCs具有正常的免疫表型,但与典型的缺血性CMSCLCs相比,NE-CMSCLCs具有更强的成骨分化潜能、快速增殖、减少衰老、减少糖酵解以及在氧化应激后产生更少的活性氧。这些差异表明,受供体健康状况的影响,NE-CMSCLCs 具有独特的功能状态。尽管它们的旁分泌组存在很大差异,但NE-CMSCLCs仍具有治疗潜力,这体现在它们能够保护缺氧/复氧损伤的人类心肌细胞,尽管效果不如典型的CMSCLCs。这项研究描述了一种独特的细胞表型,并强调了供体健康状况对自体心脏细胞疗法疗效的重要性。
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