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心脏 Sca-1 阳性细胞移植而非 c-Kit 阳性细胞移植可维持大鼠心肌梗死后存活心肌的线粒体耗氧量。

Transplantation of cardiac Sca-1-positive cells rather than c-Kit-positive cells preserves mitochondrial oxygen consumption of the viable myocardium following myocardial infarction in rats.

机构信息

Department of Molecular and Cellular Pharmacology, Tokyo University of Pharmacy and Life Sciences, 1432-1 Horinouchi, Hachioji, Tokyo 192-0392, Japan.

Department of Molecular and Cellular Pharmacology, Tokyo University of Pharmacy and Life Sciences, 1432-1 Horinouchi, Hachioji, Tokyo 192-0392, Japan.

出版信息

J Pharmacol Sci. 2019 Jul;140(3):236-241. doi: 10.1016/j.jphs.2019.07.005. Epub 2019 Jul 20.

Abstract

The cardiosphere-derived cell (CDC) is one of the candidate cells used for cardiac regenerative therapy. Cardiospheres are mixture of cells including c-Kit cells, stem cell antigen (Sca)-1 cells, and other types of cardiac progenitor cells. In this study, we compared the effect of transplantation of isolated Sca-1 cells and c-Kit cells with that of the crude CDCs (CrCDCs). Focusing on the differences in the ability for secretion of paracrine factors among 3 types of cells, we determined the effects of transplantation of these cells on cardiac intracellular signaling and mitochondrial function in rats with permanently ligated coronary arteries. We showed that the transplantation of these cells resulted in a preservation of the cardiac pump function and mitochondrial respiration at the 8th week after myocardial infarction. However, mitochondrial function in the c-Kit cell-transplanted group was lower than that in the other 2 groups. Furthermore, we found that activation levels of intracellular signaling proteins after cell transplantation may have been due to the ability of secretion of growth factors by these transplanted cell types. Our findings indicate the possibility that CrCDC and Sca-1 cells rather than c-Kit cells may be used therapeutically to preserve cardiac function and energy metabolism after myocardial infarction.

摘要

心肌球源性细胞(CDC)是用于心脏再生治疗的候选细胞之一。心肌球是包括 c-Kit 细胞、干细胞抗原(Sca)-1 细胞和其他类型的心脏祖细胞在内的细胞混合物。在这项研究中,我们比较了分离的 Sca-1 细胞和 c-Kit 细胞与粗制 CDCs(CrCDCs)移植的效果。我们关注 3 种细胞分泌旁分泌因子能力的差异,确定了这些细胞移植对永久性结扎冠状动脉大鼠心脏细胞内信号和线粒体功能的影响。结果表明,这些细胞的移植可在心肌梗死后第 8 周保存心脏泵功能和线粒体呼吸。然而,c-Kit 细胞移植组的线粒体功能低于其他 2 组。此外,我们发现细胞移植后细胞内信号蛋白的激活水平可能与这些移植细胞类型分泌生长因子的能力有关。我们的研究结果表明,CrCDC 和 Sca-1 细胞而非 c-Kit 细胞可能更适合用于治疗,以在心肌梗死后保持心脏功能和能量代谢。

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