【摘要】 心血管疾病（CVD）是全球范围内致残和致死的主要原因之一，其病理特征包括心肌细胞（CMs）不可逆性丢失、心脏纤维化及功能进行性下降。现有药物治疗和介入手段虽能缓解症状，但难以实现心肌组织的有效再生，临床需求远未满足。骨髓间充质干细胞（BMSCs）作为体内干细胞重要来源，具有增殖和多向分化等特点。体外可通过化学试剂、物理刺激、细胞因子和模拟心肌微环境以及基因转染等方法定向心肌样细胞分化。BMSCs对于心肌样细胞分化以及受损CMs的修复主要通过其自身旁分泌发挥重要作用，也可通过旁分泌产生外泌体（Exo）,Exo可携带细胞因子、磷脂和多种RNA，如微小RNA(miRNA)(miR-29b-3p/miR-125b)和长链非编码RNA(lncRNA)等通过调控含有1型血小板反应蛋白基序的解整合素样金属蛋白酶16(ADAMTS16)和去乙酰化酶7(SIRT7)等靶点，抑制CMs凋亡、减轻心肌纤维化和炎症反应。BMSCs还可作用于体内调节性T淋巴细胞（Treg），刺激其产生修复因子，促进巨噬细胞极化，通过作用自然杀伤（NK）细胞调节细胞自噬，参与免疫应答，进而减轻心肌炎症反应。现对体外诱导BMSCs定向分化为心肌样细胞的方法及相关机制以及BMSCs在糖尿病心肌病（DCM）、心肌梗死（MI）和心肌缺血-再灌注损伤（MIRI）等CVD模型中的保护作用进行综述，揭示其对CMs的保护机制，为临床应用提供借鉴。更多还原

【Abstract】 Cardiovascular disease(CVD) is one of the leading causes of disability and death worldwide. Its pathological features include irreversible loss of cardiomyocytes(CMs), cardiac fibrosis, and progressive decline in function. Although existing drug therapies and interventional measures can alleviate the symptoms, they hardly achieve effective regeneration of myocardium tissue, leaving clinical needs far from being met. The bone marrow mesenchymal stem cells(BMSCs), as an important source of endogenous stem cells, possess characteristics such as proliferation and multidirectional differentiation. In vitro, the BMSCs can be directionally differentiated into the cardiomyocyte-like cells through methods such as chemical reagents, physical stimulation, cytokines, simulation of the myocardial microenvironment, and gene transfection. The differentiation of the BMSCs into the cardiomyocyte-like cells and the repair of damaged CMs primarily rely on their paracrine effects, which also involve the production of exosomes(Exo) via paracrine signaling. The Exo can carry cytokines, phospholipids, and various RNAs, such as microRNAs(miRNA)(miR-29b-3p/miR-125b) and long non-coding RNAs(lncRNAs). They exert protective effects by regulating targets like a disintegrin and metalloproteinase with thrombospondin motifs 16(ADAMTS16) and sirtuin 7(SIRT7), thereby inhibiting CMs apoptosis and alleviating myocardial fibrosis and inflammatory responses. Furthermore, BMSCs can act on regulatory T lymphocytes(Tregs) in vivo, stimulating them to produce repair factors and promoting macrophage polarization. They also participate in immune responses by modulating natural killer(NK) cells to influence autophagy, thereby mitigating myocardial inflammatory reactions. This article reviews the methods and related mechanisms for the directional differentiation of BMSCs into the cardiomyocyte-like cells in vitro, as well as the protective effects of the BMSCs in CVD models such as diabetic cardiomyopathy(DCM), myocardial infarction(MI), and myocardial ischemia-reperfusion injury(MIRI). It aims to reveal their protective mechanisms on CMs and provide insights for clinical application.更多还原