Psaltis P J, Spoon D B, Wong D T
Department of Medicine University of Adelaide, Adelaide South Australia, Australia -
Minerva Cardioangiol. 2013 Dec;61(6):639-63.
Amongst experimental therapies being evaluated for myocardial infarction (MI), the field of cellular cardiomyoplasty still provokes much excitement, well into its second decade of investigation. Mesenchymal stromal/stem cells (MSCs) have held a particularly enduring place as one of the mainstays of adult-derived stem cell research in cardiovascular disease. These rare, non-hematopoietic cells are natively present throughout different postnatal tissues, most famously bone marrow, where they typically participate in perivascular stem cell niches and play key supportive and trophic roles. Their application for exogenous stem cell delivery is made attractive by their ease of isolation, proclivity for ex vivo expansion and potential for allogeneic use. There is now a remarkable wealth of in vitro and animal-based evidence attesting to the ability of MSCs to safely augment cardiac repair post-MI through pleiotropic mechanisms that continue to be delineated and in turn, optimised. However, despite such preclinical promise and the encouraging results of preliminary experience in human patients, the broader translation of MSCs to the clinical cardiovascular realm requires much more refinement to overcome fundamental limitations, not to mention rigorous validation to resolve lingering areas of uncertainty. Here we review the basic biological properties that have made MSCs so widely investigated for cardiovascular repair, discuss the preclinical evidence for their efficacy and purported mechanisms of action and consider the practicalities and evidence for their use in human patients with MI and cardiomyopathy.
在针对心肌梗死(MI)进行评估的实验性疗法中,细胞心肌成形术领域即便已进入研究的第二个十年,仍引发了诸多关注。间充质基质/干细胞(MSCs)作为心血管疾病中成年来源干细胞研究的主要支柱之一,一直占据着特殊且持久的地位。这些罕见的非造血细胞天然存在于不同的出生后组织中,最著名的是骨髓,它们通常在血管周围干细胞龛中发挥作用,并起到关键的支持和营养作用。它们易于分离、倾向于体外扩增以及具有同种异体使用的潜力,这使得它们在外源性干细胞递送中的应用颇具吸引力。现在有大量丰富的体外和动物实验证据表明,MSCs能够通过多种机制安全地促进心肌梗死后的心脏修复,这些机制仍在不断被阐明并进而得到优化。然而,尽管有这样的临床前前景以及在人类患者中的初步经验所取得的令人鼓舞的结果,但要将MSCs更广泛地应用于临床心血管领域,还需要进一步完善以克服基本限制,更不用说要通过严格验证来解决仍然存在的不确定性领域。在此,我们回顾了使MSCs在心血管修复方面得到广泛研究的基本生物学特性,讨论了其疗效的临床前证据及其所谓的作用机制,并考虑了其在心肌梗死和心肌病人类患者中应用的实际情况和证据。