Cardiology Division, Myongji Hospital, Kwandong University College of Medicine, Goyangsi, Gyeonggido, Republic of Korea.
Biomaterials. 2012 Feb;33(5):1376-85. doi: 10.1016/j.biomaterials.2011.10.078. Epub 2011 Nov 21.
Many approaches have shown beneficial effects of modified mesenchymal stem cells (MSCs) for treatment of infarcted myocardium, but have primarily focused on enhancing the survival of transplanted MSCs. Here, we show the dual benefits of periostin-overexpressing MSCs (p-MSCs) for infarcted myocardium. P-MSCs led to the marked histological and functional recovery of infarcted myocardium by enhancing survival of MSCs and directly preventing apoptosis of cardiomyocytes. Survival of p-MSCs themselves and cardiomyocytes co-cultured with p-MSCs or treated with the conditioned media from p-MSCs was significantly increased under hypoxic conditions. Decreases in adhesion-related integrins were reversed in cardiomyocytes co-cultured with p-MSCs, followed by increases in p-PI3K and Akt, indicating that periostin activates the PI3K pathway through adhesion-related integrins. When p-MSCs were injected into myocardial infarcted rats, histological pathology and cardiac function were significantly improved compared to MSC-injected controls. Thus, periostin might be a new target of therapeutic treatments using MSCs as carriers for infarcted myocardium.
许多方法已经证明了改良间充质干细胞（MSCs）在治疗梗死心肌方面的有益作用，但主要集中在增强移植的 MSCs 的存活率上。在这里，我们展示了外胚蛋白过表达 MSCs（p-MSCs）对梗死心肌的双重益处。p-MSCs 通过增强 MSCs 的存活并直接防止心肌细胞凋亡，显著促进了梗死心肌的组织学和功能恢复。在缺氧条件下，与 p-MSCs 共培养或用 p-MSCs 的条件培养基处理的 p-MSCs 本身和心肌细胞的存活率显著增加。与 p-MSCs 共培养的心肌细胞中与黏附相关的整合素减少得到逆转，随后 p-PI3K 和 Akt 增加，表明外胚蛋白通过与黏附相关的整合素激活 PI3K 途径。当将 p-MSCs 注射到心肌梗死大鼠中时，与 MSC 注射对照组相比，组织病理学和心功能得到显著改善。因此，外胚蛋白可能成为使用 MSCs 作为载体治疗梗死心肌的新靶点。
