The clinical use of human bone marrow–derived mesenchymal stem cells (BM-MSCs) has been hampered by their poor performance after transplantation into failing hearts. Here, to improve the therapeutic potential of BM-MSCs, we developed a strategy termed in vivo priming in which BM-MSCs are primed in vivo in myocardial infarction (MI)–induced hearts through genetically engineered hepatocyte growth factor–expressing MSCs (HGF-eMSCs) that are encapsulated within an epicardially implanted 3D cardiac patch. Primed BM-MSCs through HGF-eMSCs exhibited improved vasculogenic potential and cell viability, which ultimately enhanced vascular regeneration and restored cardiac function to the MI hearts. Histological analyses further demonstrated that the primed BM-MSCs survived longer within a cardiac patch and conferred cardioprotection evidenced by substantially higher numbers of viable cardiomyocytes in the MI hearts. These results provide compelling evidence that this in vivo priming strategy can be an effective means to enhance the cardiac repair of MI hearts.

人骨髓源性间充质干细胞（BM-MSC）的临床使用由于移植到衰竭心脏后的不良表现而受到阻碍。在这里，为了提高BM-MSC的治疗潜力，我们开发了一种称为体内启动的策略，其中BM-MSC通过基因工程表达肝细胞生长因子的MSC（HGF- eMSCs）封装在心外膜植入的3D心脏贴片中。通过HGF-eMSCs启动的BM-MSCs显示出改善的血管生成潜力和细胞活力，最终增强了血管再生并恢复了MI心脏的心脏功能。组织学分析进一步表明，引发的BM-MSC在心脏斑块中存活的时间更长，并且通过MI心脏中存活的心肌细胞数量显着增加而赋予了心脏保护作用。这些结果提供了令人信服的证据，表明这种体内启动策略可以是增强MI心脏的心脏修复的有效手段。