TY - JOUR
T1 - Transplantation of mesenchymal stem cells attenuates myocardial injury and dysfunction in a rat model of acute myocarditis
AU - Ohnishi, Shunsuke
AU - Yanagawa, Bobby
AU - Tanaka, Koichi
AU - Miyahara, Yoshinori
AU - Obata, Hiroaki
AU - Kataoka, Masaharu
AU - Kodama, Makoto
AU - Ishibashi-Ueda, Hatsue
AU - Kangawa, Kenji
AU - Kitamura, Soichiro
AU - Nagaya, Noritoshi
N1 - Funding Information:
This work was funded by a post-doctoral fellowship from the Japan Society for the Promotion of Science, and research grants for Cardiovascular Disease (16C-6, 17C-1 and 18C-1) and Human Genome Tissue Engineering 009 from the Ministry of Health, Labor and Welfare.
PY - 2007/1
Y1 - 2007/1
N2 - Acute myocarditis is a non-ischemic inflammatory disease of the myocardium for which there is currently no specific treatment. We have previously shown that mesenchymal stem cells (MSC) can ameliorate heart injury during acute ischemia and in dilated cardiomyopathy; however, the therapeutic potential in acute myocarditis is unclear. In this study, we investigated the ability of MSC to attenuate myocardial injury and dysfunction during the acute phase of experimental myocarditis. Ten-week-old male Lewis rats were injected with porcine myosin to induce myocarditis. Cultured MSC (3 × 106 cells/rat) were injected intravenously 7 days after myosin injection. At 3 weeks, myosin injection resulted in severe inflammation and significant deterioration of cardiac function. MSC transplantation attenuated increases in CD68-positive inflammatory cells and monocyte chemoattractant protein-1 (MCP-1) expression in myocardium, and improved cardiac function in this model. Furthermore, myocardial capillary density was higher in myocarditis tissue, and was further increased by MSC transplantation. In vitro, cultured adult rat cardiomyocytes were injured in response to MCP-1, whereas this effect was attenuated by MSC-derived conditioned medium, suggesting cardioprotective effects of MSC acting in a paracrine manner. MSC transplantation attenuated myocardial injury and dysfunction in a rat model of acute myocarditis, at least in part through paracrine effects of MSC.
AB - Acute myocarditis is a non-ischemic inflammatory disease of the myocardium for which there is currently no specific treatment. We have previously shown that mesenchymal stem cells (MSC) can ameliorate heart injury during acute ischemia and in dilated cardiomyopathy; however, the therapeutic potential in acute myocarditis is unclear. In this study, we investigated the ability of MSC to attenuate myocardial injury and dysfunction during the acute phase of experimental myocarditis. Ten-week-old male Lewis rats were injected with porcine myosin to induce myocarditis. Cultured MSC (3 × 106 cells/rat) were injected intravenously 7 days after myosin injection. At 3 weeks, myosin injection resulted in severe inflammation and significant deterioration of cardiac function. MSC transplantation attenuated increases in CD68-positive inflammatory cells and monocyte chemoattractant protein-1 (MCP-1) expression in myocardium, and improved cardiac function in this model. Furthermore, myocardial capillary density was higher in myocarditis tissue, and was further increased by MSC transplantation. In vitro, cultured adult rat cardiomyocytes were injured in response to MCP-1, whereas this effect was attenuated by MSC-derived conditioned medium, suggesting cardioprotective effects of MSC acting in a paracrine manner. MSC transplantation attenuated myocardial injury and dysfunction in a rat model of acute myocarditis, at least in part through paracrine effects of MSC.
KW - Acute myocarditis
KW - Cell death
KW - Cytokine
KW - Mesenchymal stem cell
KW - Paracrine effect
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U2 - 10.1016/j.yjmcc.2006.10.003
DO - 10.1016/j.yjmcc.2006.10.003
M3 - Article
C2 - 17101147
AN - SCOPUS:33845665442
SN - 0022-2828
VL - 42
SP - 88
EP - 97
JO - Journal of Molecular and Cellular Cardiology
JF - Journal of Molecular and Cellular Cardiology
IS - 1
ER -