1 Department of Musculoskeletal Biology, Faculty of Health and Life Sciences, Institute of Ageing and Chronic Disease, University of Liverpool, Liverpool, United Kingdom.
2 Institute of Genetic Medicine, Cardiovascular Research Centre, International Centre for Life, Newcastle University, Newcastle upon Tyne, United Kingdom.
Stem Cells Dev. 2019 May 1;28(9):593-607. doi: 10.1089/scd.2018.0170. Epub 2019 Apr 3.
Cardiac stem/progenitors are being used in the clinic to treat patients with a range of cardiac pathologies. However, improvements in heart function following treatment have been reported to be variable, with some showing no response. This discrepancy in response remains unresolved. Mesenchymal stem cells (MSCs) have been highlighted as a regenerative tool as these cells display both immunomodulatory and proregenerative activities. The purpose of this study was to derive a cardiac MSC population to provide an alternative/support to current therapies. We derived human cardiac-mesenchymal stem cell-like cells (CMSCLC), so named as they share some MSC characteristics. However, CMSCLC lack the MSC trilineage differentiation capacity, being capable of only rare adipogenic differentiation and demonstrating low/no osteogenic or chondrogenic potential, a phenotype that may have advantages following transplantation. Furthermore, CMSCLC expressed low levels of p16, high levels of MHCI, and low levels of MHCII. A lack of senescent cells would also be advantageous for cells to be used therapeutically, as would the ability to modulate the immune response. Crucially, CMSCLC display a transcriptional profile that includes genes associated with cardioprotective/cardiobeneficial effects. CMSCLC are also secretory and multipotent, giving rise to cardiomyocytes and endothelial cells. Our findings support CMSCLC as a novel cell population suitable for use for transplantation.
心脏干细胞/祖细胞正被用于临床治疗多种心脏病变患者。然而，治疗后的心脏功能改善情况各不相同，有些患者没有反应。这种反应差异仍未得到解决。间充质干细胞（MSCs）被认为是一种有前途的再生工具，因为这些细胞具有免疫调节和促再生活性。本研究旨在获得心脏间充质干细胞样细胞（CMSCLC），以提供替代/支持当前疗法。我们获得了人心肌间充质干细胞样细胞（CMSCLC），之所以这样命名，是因为它们具有一些 MSC 特征。然而，CMSCLC 缺乏 MSC 的三系分化能力，仅能进行罕见的脂肪生成分化，并且表现出低/无成骨或软骨形成潜力，这种表型在移植后可能具有优势。此外，CMSCLC 表达低水平的 p16、高水平的 MHCI 和低水平的 MHCII。缺乏衰老细胞对于细胞的治疗应用也是有利的，而能够调节免疫反应也是有利的。至关重要的是，CMSCLC 显示出与心脏保护/有益作用相关的基因的转录谱。CMSCLC 还具有分泌和多能性，可以产生心肌细胞和成血管细胞。我们的研究结果支持 CMSCLC 作为一种新型细胞群体，适合用于移植。
