Pattar Simranjit S, Fatehi Hassanabad Ali, Fedak Paul W M
Section of Cardiac Surgery, Department of Cardiac Sciences, Cumming School of Medicine, Libin Cardiovascular Institute of Alberta, University of Calgary, Calgary, AB, Canada.
Front Cardiovasc Med. 2019 Aug 20;6:123. doi: 10.3389/fcvm.2019.00123. eCollection 2019.
The epicardial surface of the heart is readily accessible during cardiac surgery and presents an opportunity for therapeutic intervention for cardiac repair and regeneration. As an important anatomic niche for endogenous mechanisms of repair, targeting the epicardium using decellularized extracellular matrix (ECM) bioscaffold therapy may provide the necessary environmental cues to promote functional recovery. Following ischemic injury to the heart caused by myocardial infarction (MI), epicardium derived progenitor cells (EPDCs) become activated and migrate to the site of injury. EPDC differentiation has been shown to contribute to endothelial cell, cardiac fibroblast, cardiomyocyte, and vascular smooth muscle cell populations. Post-MI, it is largely the activation of cardiac fibroblasts and the resultant dysregulation of ECM turnover which leads to maladaptive structural cardiac remodeling and loss of cardiac function. Decellularized ECM bioscaffolds not only provide structural support, but have also been shown to act as a bioactive reservoir for growth factors, cytokines, and matricellular proteins capable of attenuating maladaptive cardiac remodeling. Targeting the epicardium post-MI using decellularized ECM bioscaffold therapy may provide the necessary bioinductive cues to promote differentiation toward a pro-regenerative phenotype and attenuate cardiac fibroblast activation. There is an opportunity to leverage the clinical benefits of this innovative technology with an aim to improve the prognosis of patients suffering from progressive heart failure. An enhanced understanding of the utility of decellularized ECM bioscaffolds in epicardial repair will facilitate their growth and transition into clinical practice. This review will provide a summary of decellularized ECM bioscaffolds being developed for epicardial infarct repair in coronary artery bypass graft (CABG) surgery.
在心脏手术过程中，心脏的心外膜表面易于触及，为心脏修复和再生的治疗干预提供了机会。作为内源性修复机制的重要解剖微环境，使用脱细胞细胞外基质（ECM）生物支架疗法靶向心外膜可能提供促进功能恢复所需的环境信号。在心肌梗死（MI）导致心脏缺血性损伤后，心外膜衍生的祖细胞（EPDCs）被激活并迁移到损伤部位。EPDC分化已被证明有助于内皮细胞、心脏成纤维细胞、心肌细胞和血管平滑肌细胞群体的形成。心肌梗死后，主要是心脏成纤维细胞的激活以及由此导致的ECM周转失调，从而导致心脏结构的适应性不良重塑和心脏功能丧失。脱细胞ECM生物支架不仅提供结构支持，还被证明可作为生长因子、细胞因子和基质细胞蛋白的生物活性储存库，能够减轻适应性不良的心脏重塑。使用脱细胞ECM生物支架疗法在心肌梗死后靶向心外膜可能提供必要的生物诱导信号，以促进向促再生表型的分化并减弱心脏成纤维细胞的激活。有机会利用这项创新技术的临床益处，以改善进行性心力衰竭患者的预后。对脱细胞ECM生物支架在心外膜修复中的效用有更深入的了解将促进其发展并过渡到临床实践。本综述将总结正在开发的用于冠状动脉旁路移植术（CABG）中心外膜梗死修复的脱细胞ECM生物支架。
