Empowering adult stem cells for myocardial regeneration.
Empowering adult stem cells for myocardial regeneration.
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DOI：
10.1161/circresaha.111.243071
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发表时间：
2011-12-09
影响因子：
20.1
通讯作者：
Sussman MA
中科院分区：
文献类型：
--
作者：
Mohsin S;Siddiqi S;Collins B;Sussman MA
心力衰竭的治疗策略仍然是正在进行的研究的高度优先事项，因为临床疾病的严重未满足需求加上缺乏显著的转化进展。无论病因是急性损伤、疾病引起的慢性应激还是衰老，根本问题都是相同的：功能性心肌细胞的逐渐丧失和血流动力学输出的减少。为了避免心肌细胞损失，近年来已经采用了许多策略性方法，包括分子和细胞方法来增强心肌结构和性能。由于认识到心脏中的修复过程不足以将受损心肌恢复到正常的功能能力，并且细胞心肌成形术受到捐赠人群的存活率、增殖、植入和分化不良的阻碍，因此围绕心脏中再生医学的兴奋情绪有所缓和。为了克服这些限制，需要采用分子和细胞方法的组合，包括使用基因工程来增强对细胞死亡的抵抗力和增加再生能力。这篇综述将突出的生物学特性的方法，以加强干细胞介导的再生，以促进增强心肌再生，持久的捐赠细胞，和持久的组织修复。优化细胞递送和利用存活信号级联的力量在重新引入患者之前对干细胞进行离体遗传修饰对于提高细胞心肌成形术的功效至关重要。一旦实现了这一目标，那么基于细胞的治疗对于治疗心力衰竭具有很大的希望，以对抗与急性损伤，慢性疾病或衰老相关的心脏结构和功能的丧失。
Treatment strategies for heart failure remain a high priority for ongoing research due to the profound unmet need in clinical disease coupled with lack of significant translational progress. The underlying issue is the same whether the cause is acute damage, chronic stress from disease, or aging: progressive loss of functional cardiomyocytes and diminished hemodynamic output. To stave off cardiomyocyte losses, a number of strategic approaches have been embraced in recent years involving both molecular and cellular approaches to augment myocardial structure and performance. Resultant excitement surrounding regenerative medicine in the heart has been tempered by realizations that reparative processes in the heart are insufficient to restore damaged myocardium to normal functional capacity and that cellular cardiomyoplasty is hampered by poor survival, proliferation, engraftment and differentiation of the donated population. To overcome these limitations, a combination of molecular and cellular approaches needs to be adopted involving use of genetic engineering to enhance resistance to cell death and increase regenerative capacity. This review will highlight biological properties of approached to potentiate stem cell-mediated regeneration to promote enhanced myocardial regeneration, persistence of donated cells, and long lasting tissue repair. Optimizing cell delivery and harnessing the power of survival signaling cascades for ex vivo genetic modification of stem cells prior to reintroduction into the patient will be critical to enhance the efficacy of cellular cardiomyoplasty. Once this goal is achieved, then cell-based therapy has great promise for treatment of heart failure to combat the loss of cardiac structure and function associated with acute damage, chronic disease or aging.