Department of Pathology and Laboratory Medicine, McGovern Medical School, Houston, TX, USA; The University of Texas Health Science Center at Houston (UTHealth), Houston, TX, USA; Cardiovascular Pathology Laboratory, Texas Heart Institute, St. Luke's Episcopal Hospital, Houston, TX, USA.
J Mol Cell Cardiol. 2019 Mar;128:96-104. doi: 10.1016/j.yjmcc.2019.01.022. Epub 2019 Jan 28.
Stem cell biology has informed and energized cardiac regenerative medicine. The field is linked to a construct that challenges long-standing concepts and advances the basic tenets that: 1) the mammalian heart has the capacity for significant regeneration of cardiomyocytes (CMC) by reentry of CMC into the cell cycle and by activation of endogenous cardiac stem cells and 2) the administration of exogenous stem cell preparations can result in significant myocardial repair and regeneration in cardiac diseases. Based on the latter, major resources have been invested in clinical trials of stem cell therapy. In this review, the cardiac regenerative construct is critically analyzed. This analysis reconfirms the fundamental pathobiological realities that: 1) the mammalian heart behaves as a terminally differentiated organ with limited regenerative capacity and uncertain contribution from endogenous cardiac stem cells, 2) the healing of infarction is by scar formation, and 3) the progression of pathological myocardial remodeling produces heart failure in non-ischemic as well as ischemic disease. Some influential studies underpinning the cardiac regenerative construct now have been called into question. The efficacy of stem cell therapy to produce sustained beneficial effects in patients with ischemic and non-ischemic heart disease remains unproven. It is an open question as to whether new scientific discovery can provide a convincing rationale for further clinical trials of cardiac stem cell therapy. This should be taken into consideration in regulatory review of ongoing and future clinical trials in cardiac regenerative medicine.
干细胞生物学为心脏再生医学提供了信息和动力。该领域与一个挑战长期存在的概念并推进基本原理的构建有关：1）哺乳动物心脏具有通过心肌细胞（CMC）重新进入细胞周期和激活内源性心脏干细胞来实现 CMC 大量再生的能力，以及 2）外源性干细胞制剂的给药可导致心脏疾病中的心肌修复和再生显著改善。基于后者，大量资源已投入到干细胞治疗的临床试验中。在这篇综述中，心脏再生构建体受到了批判性分析。这种分析再次证实了基本的病理生物学现实：1）哺乳动物心脏表现为终末分化器官，具有有限的再生能力和内源性心脏干细胞的不确定贡献，2）梗塞的愈合是通过疤痕形成，以及 3）病理性心肌重构的进展导致非缺血性和缺血性疾病中的心力衰竭。一些支持心脏再生构建体的有影响力的研究现在已经受到质疑。干细胞疗法在缺血性和非缺血性心脏病患者中产生持续有益效果的疗效尚未得到证实。新的科学发现是否能为进一步的心脏干细胞治疗临床试验提供令人信服的理由，这仍是一个悬而未决的问题。在心脏再生医学中，正在进行和未来的临床试验的监管审查中应考虑到这一点。
