间充质干细胞治疗心肌梗死的研究进展

doi:10.16352/j.issn.1001-6325.2023.01.0021

摘要/Abstract

摘要： 急性心肌梗死(AMI)是由冠状动脉闭塞引起的缺血性心肌坏死,无法通过心肌细胞再生进行自我修复,坏死心肌被纤维瘢痕替代,引发心室重塑,最终导致心力衰竭。诸多临床前和临床研究证实间充质干细胞(MSCs)移植治疗AMI的安全性和有效性。MSCs由多向分化潜能、能够调节氧化应激、分泌多种细胞因子和生长因子的异质性细胞组成,在移植过程中通过转分化、细胞融合和旁分泌等途径发挥其免疫调节、血管生成、抗炎和抗凋亡等作用。迄今已有多种移植途径输注MSCs,包括心肌内注射、经冠状动脉内注射、经静脉注射等。此外,移植的细胞剂量、时机等均是影响MSCs治疗效果的重要因素。然而,MSCs移植后在梗死心肌中的滞留率和存活率均很低,进而限制其进一步发挥作用,也是导致其向临床转化应用的重要瓶颈和障碍。针对上述问题,近年来诸多研究提出新理念、新策略、新技术和新方法,如细胞预处理、优化梗死局部微环境、联合基因治疗或组织工程技术、外泌体输注、靶向移植干细胞及其外泌体等,显著提高了MSCs的移植效率和治疗效果,为干细胞修复梗死心肌的研究和转化揭开新的篇章。本文对近年来MSCs修复梗死心肌的进展做一综述。

关键词: 间充质干细胞, 心肌梗死, 外泌体

Abstract: Acute myocardial infarction (AMI) is an ischemic myocardial necrosis caused by coronary artery occlusion, which can't be self-repaired through cardiomyocyte regeneration. The necrotic myocardium is replaced by fibrous scars during ventricular remodeling, ultimately leading to heart failure. The safety and efficacy of mesenchymal stem cells (MSCs) transplantation after AMI have been demonstrated by numerous preclinical and clinical studies. MSCs are composed of heterogeneous cells with multi-directional differentiation potential, which can regulate oxidative stress, and secrete a variety of cytokines and growth factors. After being implanted in vivo, MSCs play their roles in immunomodulatory, angiogenesis, anti-inflammatory, and anti-apoptosis through trans-differentiation, cell fusion, and paracrine. Currently, there has been a variety of access to implant MSCs, including intramyocardial injection, intracoronary infusion, and intravenous injection. In addition, the dose and timing of transplantation are also important factors affecting the therapeutic effect of MSCs. However, the low retention and survival rates of MSCs in infarcted myocardium after being transplanted limit their further effect and hinder their clinical translation. In recent years, new concepts, strategies, technologies, and methods for MSCs treatment have been proposed, including cell preconditioning, optimization of the infract local microenvironment, combined gene therapy or tissue engineering technology, exosome infusion, and targeted transplantation of stem cells and their exosomes, which significantly improve the transplantation efficiency and therapeutic effect of MSCs, and open a new chapter for the research and transformation of stem cells to repair the infarcted myocardium. This article reviews the progress of MSCs in repairing myocardial infarction in recent years.

Key words: mesenchymal stem cells, myocardial infarction, exosome

中图分类号:

R541.4

姜俣, 钱海燕. 间充质干细胞治疗心肌梗死的研究进展[J]. 基础医学与临床, 2023, 43(1): 21-29.

JIANG Yu, QIAN Haiyan. Progress in application of mesenchymal stem cells in treatment of acute myocardial infarction[J]. Basic & Clinical Medicine, 2023, 43(1): 21-29.

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