Laboratorio di Biologia Vascolare e Medicina Rigenerativa, Via Parea 4, I-2018 Milan, Italy.
Cardiovasc Res. 2011 Feb 1;89(2):362-73. doi: 10.1093/cvr/cvq292. Epub 2010 Sep 10.
The heart contains c-kit(+) progenitors that maintain cardiac homeostasis. Cardiac c-kit(+) cells are multipotent and give rise to myocardial, endothelial and smooth muscle cells, both in vitro and in vivo. C-kit(+) cells have been thoroughly investigated for their stem cell activity, susceptibility to stress conditions and ageing, as well as for their ability to repair the infarcted heart. Recently, expression of mesenchymal stem cell (MSC) markers and MSC differentiation potency have been reported in cardiac progenitor cells. Based on this evidence, we hypothesized that c-kit(+) cells may have phenotypic and functional features in common with cardiac MSCs.
Culture of cells obtained from enzymatic dissociation of heart auricle fragments produced a fast-growing fibroblast-like population expressing mesenchymal markers. C-kit(+) cells co-expressing MSC markers were identified in this population, sorted by flow cytometry and cultured in the presence or the absence of unselected cardiac cells from the same patients. Subsets of c-kit(+) cells also co-expressed MSCs markers in vivo, as detected by immunofluorescence analysis of auricle tissue. Ex vivo expanded c-kit(+) cells produced osteoblasts and adipocytes, although less preferentially than bone marrow-derived MSCs, possessed vascular smooth muscle cell features and were induced to differentiate into endothelium-like and cardiac-like cells.
In line with previous findings, our results indicate that c-kit(+) cardiac progenitors are primitive stem cells endowed with multilineage differentiation ability. They further suggest a possible relationship between these cells and a heart-specific MSC population with cardiovascular commitment potential.
心脏含有维持心脏内稳态的 c-kit(+)祖细胞。心脏 c-kit(+)细胞具有多能性，并在体外和体内产生心肌、内皮和平滑肌细胞。c-kit(+)细胞的干细胞活性、对应激条件和衰老的敏感性以及修复梗死心脏的能力已经得到了彻底的研究。最近，心脏祖细胞中报告了间充质干细胞 (MSC) 标志物的表达和 MSC 分化潜能。基于这一证据，我们假设 c-kit(+)细胞可能具有与心脏 MSC 共同的表型和功能特征。
从心脏耳状部片段酶解获得的细胞培养产生了快速生长的成纤维样细胞群体，表达间充质标志物。在该群体中鉴定出共表达 MSC 标志物的 c-kit(+)细胞，通过流式细胞术分选，并在存在或不存在来自同一患者的未分选心脏细胞的情况下进行培养。通过对耳组织的免疫荧光分析，在体内也检测到 c-kit(+)细胞亚群共表达 MSC 标志物。体外扩增的 c-kit(+)细胞产生成骨细胞和脂肪细胞，尽管不如骨髓来源的 MSC 那样优先，但具有血管平滑肌细胞特征，并被诱导分化为内皮样和心肌样细胞。
与先前的发现一致，我们的结果表明 c-kit(+)心脏祖细胞是具有多谱系分化能力的原始干细胞。它们进一步表明这些细胞与具有心血管定向潜能的心脏特异性 MSC 群体之间可能存在关系。
