Department of Pharmacology, University Medical Center Göttingen, Georg-August-University Göttingen, Goettingen, Germany.
J Mol Cell Cardiol. 2011 Feb;50(2):320-6. doi: 10.1016/j.yjmcc.2010.10.027. Epub 2010 Oct 30.
Cardiac muscle engineering is evolving rapidly and may ultimately be exploited to (1) model cardiac development, physiology, and pathology; (2) identify and validate drug targets; (3) assess drug safety and efficacy; and (4) provide therapeutic substitute myocardium. The ultimate success in any of these envisioned applications depends on the utility of human cells and their assembly into myocardial equivalents with structural and functional properties of mature heart muscle. Embryonic stem cells appear as a promising cell source in this respect, because they can be cultured reliably and differentiated robustly into cardiomyocytes. Despite their unambiguous cardiogenicity, data on advanced maturation and seamless myocardial integration of embryonic stem cell-derived cardiomyocytes in vivo are sparse. Additional concerns relate to the limited control over cardiomyogenic specification and cardiomyocyte maturation in vitro as well as the risk of teratocarcinoma formation and immune rejection of stem cell implants in vivo. Through the invent of embryonic-like stem cells - such as parthenogenetic stem cells, male germline stem cells, and induced pluripotent stem cells - some but certainly not all of these issues may be addressed, albeit at the expense of additional concerns. This review will discuss the applicability of embryonic and embryonic-like stem cells in myocardial tissue engineering and address issues that require particular attention before the potential of stem cell-based heart muscle engineering may be fully exploited. This article is part of a special issue entitled, "Cardiovascular Stem Cells Revisited".
心肌工程学正在迅速发展,最终可能被用于:(1) 模拟心脏发育、生理学和病理学;(2) 鉴定和验证药物靶点;(3) 评估药物安全性和疗效;以及 (4) 提供治疗性替代心肌。这些预期应用中的任何一项的最终成功都取决于人类细胞的效用及其组装成具有成熟心肌结构和功能特性的心肌等效物。胚胎干细胞在这方面似乎是一种很有前途的细胞来源,因为它们可以可靠地培养,并强有力地分化为心肌细胞。尽管胚胎干细胞具有明确的心脏生成能力,但关于胚胎干细胞来源的心肌细胞在体内的高级成熟和无缝心肌整合的数据仍然很少。此外,还存在一些问题,包括对体外心肌生成特异性和心肌细胞成熟的控制有限,以及体内畸胎瘤形成和干细胞植入免疫排斥的风险。通过发明胚胎样干细胞——如孤雌生殖干细胞、雄性生殖干细胞和诱导多能干细胞——可以解决其中一些问题,但肯定不是所有问题,尽管这需要付出额外的代价。这篇综述将讨论胚胎和胚胎样干细胞在心肌组织工程中的适用性,并讨论在充分利用基于干细胞的心肌工程的潜力之前需要特别关注的问题。本文是题为“心血管干细胞再探讨”的特刊的一部分。