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The role of regenerative therapy in the treatment of right ventricular failure: a literature review
Stem Cell Research & Therapy ( IF 7.1 ) Pub Date : 2020-11-25 , DOI: 10.1186/s13287-020-02022-w
Christoph Haller , Mark K. Friedberg , Michael A. Laflamme

Right ventricular (RV) failure is a commonly encountered problem in patients with congenital heart disease but can also be a consequence of left ventricular disease, primary pulmonary hypertension, or RV-specific cardiomyopathies. Improved survival of the aforementioned pathologies has led to increasing numbers of patients suffering from RV dysfunction, making it a key contributor to morbidity and mortality in this population. Currently available therapies for heart failure were developed for the left ventricle (LV), and there is clear evidence that LV-specific strategies are insufficient or inadequate for the RV. New therapeutic strategies are needed to address this growing clinical problem, and stem cells show significant promise. However, to properly evaluate the prospects of a potential stem cell-based therapy for RV failure, one needs to understand the unique pathophysiology of RV dysfunction and carefully consider available data from animal models and human clinical trials. In this review, we provide a comprehensive overview of the molecular mechanisms involved in RV failure such as hypertrophy, fibrosis, inflammation, changes in energy metabolism, calcium handling, decreasing RV contractility, and apoptosis. We also summarize the available preclinical and clinical experience with RV-specific stem cell therapies, covering the broad spectrum of stem cell sources used to date. We describe two different scientific rationales for stem cell transplantation, one of which seeks to add contractile units to the failing myocardium, while the other aims to augment endogenous repair mechanisms and/or attenuate harmful remodeling. We emphasize the limitations and challenges of regenerative strategies, but also highlight the characteristics of the failing RV myocardium that make it a promising target for stem cell therapy.

中文翻译:

再生疗法在右室衰竭治疗中的作用:文献综述

先天性心脏病患者通常会遇到右心室(RV)衰竭的问题,但也可能是左心室疾病,原发性肺动脉高压或RV特异性心肌病的结果。上述病理学的改善的存活率导致患有RV功能障碍的患者数量增加,使其成为该人群发病率和死亡率的关键因素。针对左心室(LV)开发了目前可用的心力衰竭治疗方法,并且有明确的证据表明,针对LV的LV特异性策略不足或不足。需要新的治疗策略来解决这一日益严重的临床问题,而干细胞具有广阔的前景。但是,为了正确评估基于干细胞的右室衰竭治疗的前景,人们需要了解RV功能异常的独特病理生理学,并仔细考虑来自动物模型和人类临床试验的可用数据。在这篇综述中,我们提供了与RV衰竭有关的分子机制的全面概述,例如肥大,纤维化,炎症,能量代谢变化,钙处理,RV收缩力降低和细胞凋亡。我们还总结了RV特异性干细胞疗法的可用临床前和临床经验,涵盖了迄今为止使用的广泛的干细胞来源。我们描述了干细胞移植的两种不同的科学原理,其中一种旨在为衰竭的心肌增加收缩单位,而另一种旨在增强内源性修复机制和/或减轻有害的重塑。
更新日期:2020-11-26
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