Department of Pediatrics, Graduate School of Medicine, Hokkaido University, Kita-15, Nishi 7, Kita-ku, Sapporo, 060-8638, Japan.
MRC Mitochondrial Biology Unit, University of Cambridge, Cambridge, UK.
Sci Rep. 2022 Mar 22;12(1):4344. doi: 10.1038/s41598-022-08583-5.
Given the potential for myocardial stem cell transplantation as a promising treatment for heart failure, numerous clinical trials have been conducted and its usefulness has been clearly confirmed. However, the low rate of engraftment of transplanted cells has become a clinical problem, and this needs to be improved in the case of transplanting cells to the heart. To address this issue, we report on attempts to prepare mitochondria-activated stem cells (MITO cells) for use in transplantation. MITO cells, which is cardiac progenitor cells (CPCs) activated by the mitochondrial delivery of resveratrol with an anti-oxidant and mitochondrial activation effects were successfully prepared using a mitochondrial targeting nanocarrier (MITO-Porter). The purpose of this study was to validate the therapeutic effect of cell transplantation by the MITO cells using a mouse model of myocardial ischemia-reperfusion. Mouse CPCs were used as transplanted cells. The transplantation of CPCs and MITO cells were conducted after myocardial ischemia-reperfusion, and the therapeutic effect was determined. The MITO cells transplanted group showed increase in postoperative weight gain, improve cardiac function and inhibition of fibrosis compared to the non-transplanted group and the CPC group. The transplantation of MITO cells to the ischemic myocardium showed a stronger transplantation effect compared to conventional CPC transplantation.
鉴于心肌干细胞移植作为心力衰竭有前途的治疗方法的潜力，已经进行了许多临床试验，其有效性已得到明确证实。然而，移植细胞的植入率低已成为临床问题，这在心脏移植细胞的情况下需要加以改进。为了解决这个问题，我们报告了尝试制备线粒体激活的干细胞（MITO 细胞）用于移植的情况。MITO 细胞是通过用具有抗氧化和线粒体激活作用的白藜芦醇递送至线粒体激活的心脏祖细胞（CPCs），使用线粒体靶向纳米载体（MITO-Porter）成功制备的。本研究的目的是使用心肌缺血再灌注的小鼠模型来验证 MITO 细胞移植的治疗效果。使用小鼠 CPC 作为移植细胞。在心肌缺血再灌注后进行 CPC 和 MITO 细胞的移植，并确定治疗效果。与未移植组和 CPC 组相比，MITO 细胞移植组在术后体重增加、改善心功能和抑制纤维化方面表现出更高的疗效。与传统的 CPC 移植相比，将 MITO 细胞移植到缺血心肌中显示出更强的移植效果。
