通过间充质干细胞的旁分泌作用激活心脏祖细胞。

Activation of cardiac progenitor cells through paracrine effects of mesenchymal stem cells.

作者信息

Nakanishi Chiaki, Yamagishi Masakazu, Yamahara Kenichi, Hagino Ikuo, Mori Hidezo, Sawa Yoshiki, Yagihara Toshikatsu, Kitamura Soichiro, Nagaya Noritoshi

机构信息

Department of Regenerative Medicine and Tissue Engineering, National Cardiovascular Center Research Institute, 5-7-1 Fujishirodai, Suita, Osaka 565-8565, Japan.

出版信息

Biochem Biophys Res Commun. 2008 Sep 12;374(1):11-6. doi: 10.1016/j.bbrc.2008.06.074. Epub 2008 Jun 27.

DOI:10.1016/j.bbrc.2008.06.074

PMID:18586003

Abstract

Mesenchymal stem cells (MSC) transplantation has been proved to be promising strategy to treat the failing heart. The effect of MSC transplantation is thought to be mediated mainly in a paracrine manner. Recent reports have suggested that cardiac progenitor cells (CPC) reside in the heart. In this study, we investigated whether MSC had paracrine effects on CPC in vitro. CPC were isolated from the neonatal rat heart using an explant method. MSC were isolated from the adult rat bone marrow. MSC-derived conditioned medium promoted proliferation of CPC and inhibited apoptosis of CPC induced by hypoxia and serum starvation. Chemotaxis chamber assay demonstrated that MSC-derived conditioned medium enhanced migration of CPC. Furthermore, MSC-derived conditioned medium upregulated expression of cardiomyocyte-related genes in CPC such as beta-myosin heavy chain (beta-MHC) and atrial natriuretic peptide (ANP). In conclusion, MSC-derived conditioned medium had protective effects on CPC and enhanced their migration and differentiation.

摘要

间充质干细胞（MSC）移植已被证明是治疗衰竭心脏的一种有前景的策略。MSC移植的效果被认为主要是以旁分泌方式介导的。最近的报道表明心脏祖细胞（CPC）存在于心脏中。在本研究中，我们调查了MSC在体外对CPC是否具有旁分泌作用。采用组织块培养法从新生大鼠心脏中分离出CPC。从成年大鼠骨髓中分离出MSC。MSC条件培养基促进了CPC的增殖，并抑制了缺氧和血清饥饿诱导的CPC凋亡。趋化小室试验表明，MSC条件培养基增强了CPC的迁移。此外，MSC条件培养基上调了CPC中与心肌细胞相关基因的表达，如β-肌球蛋白重链（β-MHC）和心钠素（ANP）。总之，MSC条件培养基对CPC具有保护作用，并增强了它们的迁移和分化。