Electrical stimulation to optimize cardioprotective exosomes from cardiac stem cells.
Electrical stimulation to optimize cardioprotective exosomes from cardiac stem cells.
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DOI：
10.1016/j.mehy.2015.12.022
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发表时间：
2016-03
影响因子：
4.7
通讯作者：
Tang YL
中科院分区：
文献类型：
--
作者：
Campbell CR;Berman AE;Weintraub NL;Tang YL
受伤或缺血的心脏组织具有有限的内在再生能力。虽然干细胞移植是刺激心脏修复的一种很有前途的方法，但它在人类身上的成功迄今为止是有限的。利用干细胞的治疗效益需要更好地了解其作用机制和优化其功能的方法。心脏干细胞（CSC）是一种特别有效的心脏修复细胞来源，电刺激预处理CSC （EleS）被证明可以进一步增强其功能，尽管其机制尚不清楚。最近的研究表明，移植干细胞主要通过释放含有心脏保护分子（如miRNAs）的外泌体与内源性组织沟通来发挥其作用，这些外泌体被受体细胞摄取后可能刺激存活、增殖和血管生成。外泌体也是分离的有效治疗剂，可能为干细胞移植提供一种可行的替代方案。我们假设EleS通过其对心脏保护外泌体产生的有益作用来增强csc介导的心脏修复。此外，我们假设双心室起搏对心力衰竭患者的有益作用可能部分源于es诱导的内源性CSC预处理以促进心脏修复。在未来的研究中，我们的假设可能为优化干细胞治疗和增强当前的起搏方案提供应用，这可能会显著推进心脏病患者的治疗。
Injured or ischemic cardiac tissue has limited intrinsic capacity for regeneration. While stem cell transplantation is a promising approach to stimulating cardiac repair, its success in humans has thus far been limited. Harnessing the therapeutic benefits of stem cells requires a better understanding of their mechanisms of action and methods to optimize their function. Cardiac stem cells (CSC) represent a particularly effective cellular source for cardiac repair, and pre-conditioning CSC with electrical stimulation (EleS) was demonstrated to further enhance their function, although the mechanisms are unknown. Recent studies suggest that transplanted stem cells primarily exert their effects through communicating with endogenous tissues via the release of exosomes containing cardioprotective molecules such as miRNAs, which upon uptake by recipient cells may stimulate survival, proliferation, and angiogenesis. Exosomes are also effective therapeutic agents in isolation and may provide a feasible alternative to stem cell transplantation. We hypothesize that EleS enhances CSC-mediated cardiac repair through its beneficial effects on production of cardioprotective exosomes. Moreover, we hypothesize that the beneficial effects of biventricular pacing in patients with heart failure may in part result from EleS-induced preconditioning of endogenous CSC to promote cardiac repair. With future research, our hypothesis may provide applications to optimize stem cell therapy and augment current pacing protocols, which may significantly advance the treatment of patients with heart disease.