心肌纤维化：肌成纤维细胞介导的病理调节和药物传递策略。
Cardiac fibrosis: Myofibroblast-mediated pathological regulation and drug delivery strategies.
机构信息
Department of Molecular Biomedical Sciences, North Carolina State University, NC, USA; Joint Department of Biomedical Engineering, University of North Carolina at Chapel Hill and North Carolina State University, USA.
Department of Molecular Biomedical Sciences, North Carolina State University, NC, USA; Joint Department of Biomedical Engineering, University of North Carolina at Chapel Hill and North Carolina State University, USA.
出版信息
Adv Drug Deliv Rev. 2021 Jun;173:504-519. doi: 10.1016/j.addr.2021.03.021. Epub 2021 Apr 5.
Cardiac fibrosis remains an unresolved problem in heart diseases. After initial injury, cardiac fibroblasts (CFs) are activated and subsequently differentiate into myofibroblasts (myoFbs) that are major mediator cells in the pathological remodeling. MyoFbs exhibit proliferative and secretive characteristics, and contribute to extracellular matrix (ECM) turnover, collagen deposition. The persistent functions of myoFbs lead to fibrotic scars and cardiac dysfunction. The anti-fibrotic treatment is hindered by the elusive mechanism of fibrosis and lack of specific targets on myoFbs. In this review, we will outline the progress of cardiac fibrosis and its contributions to the heart failure. We will also shed light on the role of myoFbs in the regulation of adverse remodeling. The communication between myoFbs and other cells that are involved in the heart injury and repair respectively will be reviewed in detail. Then, recently developed therapeutic strategies to treat fibrosis will be summarized such as i) chimeric antigen receptor T cell (CAR-T) therapy with an optimal target on myoFbs, ii) direct reprogramming from stem cells to quiescent CFs, iii) "off-target" small molecular drugs. The application of nano/micro technology will be discussed as well, which is involved in the construction of cell-based biomimic platforms and "pleiotropic" drug delivery systems.
心肌纤维化仍然是心脏病领域尚未解决的问题。在初始损伤后，心肌成纤维细胞（CFs）被激活，随后分化为肌成纤维细胞（myoFbs），它们是病理性重构的主要调节细胞。myoFbs 具有增殖和分泌特性，参与细胞外基质（ECM）的转换和胶原沉积。myoFbs 的持续功能导致纤维疤痕和心脏功能障碍。抗纤维化治疗受到纤维化机制难以捉摸和缺乏针对 myoFbs 的特异性靶点的阻碍。在这篇综述中，我们将概述心肌纤维化的进展及其对心力衰竭的贡献。我们还将阐明 myoFbs 在调节不良重构中的作用。将详细讨论 myoFbs 与参与心脏损伤和修复的其他细胞之间的通讯。然后，我们将总结最近开发的治疗纤维化的治疗策略，例如 i）针对 myoFbs 的嵌合抗原受体 T 细胞（CAR-T）治疗，ii）干细胞向静止 CFs 的直接重编程，iii）“脱靶”小分子药物。还将讨论纳米/微技术的应用，涉及基于细胞的仿生平台和“多效”药物输送系统的构建。
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