Istituto di Anatomia Patologica, Università degli Studi di Udine, P.zzle S. Maria della Misericordia, 33100 Udine, Italy.
Experimental Cardiovascular Medicine, Regenerative Medicine Section, Bristol Heart Institute, School of Clinical Sciences, University of Bristol, Level 7, Bristol Royal Infirmary, Upper Maudlin Street, Bristol BS2 8HW, United Kingdom.
Pharmacol Res. 2018 Jan;127:101-109. doi: 10.1016/j.phrs.2017.05.023. Epub 2017 May 31.
Clinical data and basic research indicate that the structural and functional alterations that characterize the evolution of cardiac disease towards heart failure may be, at least in part, reversed. This paradigm shift is due to the accumulation of evidence indicating that, in peculiar settings, cardiomyocytes may be replenished. Moving from the consideration that cardiomyocytes are rapidly withdrawn from the cell cycle after birth, independent laboratories have tested the hypothesis that cardiac resident stem/progenitor cells resided in mammalian hearts and were important for myocardial repair. After almost two decades of intensive investigation, several (but partially overlapping) cardiac resident stem/progenitor cell populations have been identified. These primitive cells are characterized by mesenchymal features, unique properties that distinguish them from mesodermal progenitors residing in other tissues, and heterogeneous embryological origins (that include the neural crest and the epicardium). A further layer of complexity is related to the nature, in vivo localization and properties of mesodermal progenitors residing in adult tissues. Intriguingly, these latter, whose possible perivascular pericyte/mural cell origin has been shown, have been identified in human hearts too. However, their exact anatomical localization, pathophysiological role, and their relationship with cardiac stem/progenitor cells are emerging only recently. Therefore, aim of this review is to discuss the different origin, the distinct nature, and the complementary effect of cardiac stem cells and pericytes supporting regenerative strategies based on the combined use of both myogenic and angiogenic factors.
临床数据和基础研究表明,心脏疾病向心力衰竭发展的结构和功能改变至少在部分程度上是可以逆转的。这种范式转变源于越来越多的证据表明,在特定环境下,心肌细胞可能会得到补充。人们最初认为心肌细胞在出生后很快就会退出细胞周期,此后独立实验室检验了这样一种假设,即心脏固有干细胞/祖细胞存在于哺乳动物心脏中,并对心肌修复很重要。经过近二十年的深入研究,已经确定了几种(但部分重叠)心脏固有干细胞/祖细胞群体。这些原始细胞具有间质特征,这些独特的特性将它们与存在于其他组织中的中胚层祖细胞区分开来,而且它们具有不同的胚胎起源(包括神经嵴和心外膜)。更为复杂的是,存在于成体组织中的中胚层祖细胞的性质、体内定位和特性。有趣的是,这些祖细胞可能起源于血管周围的周细胞/壁细胞,在人类心脏中也被发现了。然而,它们的确切解剖定位、病理生理学作用以及它们与心脏干细胞/祖细胞的关系最近才被揭示出来。因此,本文旨在讨论心脏干细胞和周细胞的不同起源、不同性质以及它们在基于联合使用肌生成和血管生成因子的再生策略中的互补作用。