Human Neonatal Cardiovascular Progenitors: Unlocking the Secret to Regenerative Ability

Although clinical benefit can be achieved after cardiac transplantation of adult c-kit+ or cardiosphere-derived cells for myocardial repair, these stem cells lack the regenerative capacity unique to neonatal cardiovascular stem cells. Unraveling the molecular basis for this age-related discrepancy in function could potentially transform cardiovascular stem cell transplantation. In this report, clonal populations of human neonatal and adult cardiovascular progenitor cells were isolated and characterized, revealing the existence of a novel subpopulation of endogenous cardiovascular stem cells that persist throughout life and co-express both c-kit and isl1. Epigenetic profiling identified 41 microRNAs whose expression was significantly altered with age in phenotypically-matched clones. These differences were correlated with reduced proliferation and a limited capacity to invade in response to growth factor stimulation, despite high levels of growth factor receptor on progenitors isolated from adults. Further understanding of these differences may provide novel therapeutic targets to enhance cardiovascular regenerative capacity.

尽管将成人c-kit阳性（c-kit+）或心球来源细胞用于心肌修复的心脏移植可获得临床收益，但这类干细胞缺乏新生儿心血管干细胞所特有的再生能力。阐明这种功能上的年龄相关差异的分子基础，有望推动心血管干细胞移植领域的变革。本研究中，研究人员对人类新生儿与成人的心血管祖细胞克隆群体进行了分离与鉴定，发现了一种全新的内源性心血管干细胞亚群：这类细胞终生存在，且可同时表达c-kit与isl1。表观遗传谱分析鉴定出41种微小RNA，在表型匹配的克隆中，它们的表达水平随年龄发生了显著变化。尽管从成人分离的祖细胞表面生长因子受体表达水平较高，但这些表达差异与增殖能力下降、以及生长因子刺激下的侵袭能力受限密切相关。对这些差异的进一步解析，有望为增强心血管再生能力提供全新的治疗靶点。