Resident human cardiac stem cells: role in cardiac cellular homeostasis and potential for myocardial regeneration.
Resident human cardiac stem cells: role in cardiac cellular homeostasis and potential for myocardial regeneration.
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DOI：
10.1038/ncpcardio0409
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发表时间：
2006-03-01
影响因子：
--
通讯作者：
Nadal-Ginard, Bernardo
中科院分区：
文献类型：
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作者：
Torella, Daniele;Ellison, Georgina M;Nadal-Ginard, Bernardo
目前心肌梗死的治疗方法已显著降低了缺血性心肌病的急性死亡率。这种减少导致了一大批患者的存活，这些患者留下了明显的“心肌细胞缺陷”。一旦这种缺陷导致心力衰竭，就没有可用的治疗方法来改善长期的心功能。干细胞生物学的最新进展集中在再生收缩心肌组织的可能性上。这些方法中的大多数都需要移植外源心脏再生细胞。最近，我们和其他人报道了成年哺乳动物的心肌，包括人类的心肌，含有少量的心脏干细胞和祖细胞(CSCs)，可以补充心肌细胞数量，在某些情况下，还可以补充冠脉微循环。人类CSCs(HCSCs)参与维持心肌细胞终生稳态，并参与心脏病理重塑。它们可以被分离、繁殖和克隆。单细胞克隆的后代在体外和体内分化为肌细胞、血管内皮细胞和平滑肌细胞。令人惊讶的是，在应对不同形式的压力时，hCSCs会获得一种衰老的、功能失调的表型。值得注意的是，这些无功能的CSC约占老年人CSC总数的50%--这些人最有可能是基于HCSC的心肌再生的候选者。因此，开发临床上有效的心肌再生治疗方法具有双重挑战：在原位产生hCSCs的激活以避免细胞移植的需要，以及阐明导致HCSC衰老的机制以防止或逆转其发展。
Current treatments for myocardial infarction have significantly reduced the acute mortality of ischemic cardiomyopathy. This reduction has resulted in the survival of a large cohort of patients left with a significant 'myocyte deficit'. Once this deficit leads to heart failure there is no available therapy to improve long-term cardiac function. Recent developments in stem cell biology have focused on the possibility of regenerating contractile myocardial tissue. Most of these approaches have entailed the transplantation of exogenous cardiac-regenerating cells. Recently, we and others have reported that the adult mammalian myocardium, including that in humans, contains a small pool of cardiac stem and progenitor cells (CSCs) that can replenish the cardiomyocyte population and, in some cases, the coronary microcirculation. The human CSCs (hCSCs) are involved in maintaining myocardial cell homeostasis throughout life and participate in remodeling in cardiac pathology. They can be isolated, propagated and cloned. The progeny of a single cell clone differentiates in vitro and in vivo into myocytes, smooth muscle and endothelial cells. Surprisingly, in response to different forms of stress, hCSCs acquire a senescent, dysfunctional phenotype. Strikingly, these nonfunctional CSCs constitute around 50% of the total CSC pool in older individuals-those most likely to be candidates for hCSC-based myocardial regeneration. Therefore, the challenge to develop clinically effective therapies of myocardial regeneration is twofold: to produce the activation of the hCSCs in situ in order to obviate the need for cell transplantation, and to elucidate the mechanisms responsible for hCSC senescence in order to prevent or reverse its development.