It has been reported that transplanting native cells would lack efficiency without producing artificial cell-tissue, due to the exaggerated oxidative stress in doxorubicin-induced cardiomyopathy. We attempted to activate cardiac progenitor cells (CPCs) by delivering resveratrol to mitochondria using a mitochondrial drug delivery system (MITO-Porter system). We first evaluated the viability of H9c2 cells (a cardio myoblast cell line) after doxorubicin treatment, where H9c2 cells were co-cultured with or without the mitochondria activated CPCs (referred to herein as MITO cell). We next evaluated the survival rate of doxorubicin treated mice, with or without the injection of MITO cells into the myocardium. Finally, we examined the molecular mechanism of the cell therapy by detecting oxidative stress and the induction of apoptosis in addition to quantification of the mRNA and protein levels about oxidative phosphorylation (OXPHOS). The MITO cell transplanted mice lived significantly longer than the conventional CPC transplanted ones. Oxidative stress and massive cell death were both significantly reduced in the MITO cell transplanted hearts, in which the expression levels of OXPHOS protein and gene were also higher than the control group. In doxorubicin-induced cardiomyopathy, the transplantation of MITO cells, which possess activated mitochondria, is more efficient compared to conventional CPC transplantation.

据报道，由于阿霉素诱导的心肌病中的过度氧化应激，移植天然细胞将缺乏效率而不产生人工细胞组织。我们试图通过使用线粒体药物递送系统（MITO-Porter系统）将白藜芦醇递送至线粒体来激活心脏祖细胞（CPC）。我们首先评估了阿霉素处理后H9c2细胞（心脏成肌细胞系）的活力，其中将H9c2细胞与或不与线粒体激活的CPCs（在本文中称为MITO细胞）共培养。接下来，我们评估了经过或不经过MITO细胞注射到心肌中的阿霉素治疗小鼠的存活率。最后，我们通过检测氧化应激和细胞凋亡的诱导，以及对氧化磷酸化（OXPHOS）的mRNA和蛋白质水平进行定量分析，从而研究了细胞疗法的分子机制。与传统的CPC移植相比，MITO细胞移植的小鼠的寿命明显更长。MITO细胞移植心脏的氧化应激和大量细胞死亡均显着降低，其中OXPHOS蛋白和基因的表达水平也高于对照组。在阿霉素诱导的心肌病中，具有活化线粒体的MITO细胞的移植比常规的CPC移植更有效。与传统的CPC移植相比，MITO细胞移植的小鼠的寿命明显更长。MITO细胞移植心脏的氧化应激和大量细胞死亡均显着降低，其中OXPHOS蛋白和基因的表达水平也高于对照组。在阿霉素诱导的心肌病中，具有活化线粒体的MITO细胞的移植比常规的CPC移植更有效。与传统的CPC移植相比，MITO细胞移植的小鼠的寿命明显更长。MITO细胞移植心脏的氧化应激和大量细胞死亡均显着降低，其中OXPHOS蛋白和基因的表达水平也高于对照组。在阿霉素诱导的心肌病中，具有活化线粒体的MITO细胞的移植比常规的CPC移植更有效。