PMID- 17101147 OWN - NLM STAT- MEDLINE DCOM- 20070227 LR - 20141120 IS - 0022-2828 (Print) IS - 0022-2828 (Linking) VI - 42 IP - 1 DP - 2007 Jan TI - Transplantation of mesenchymal stem cells attenuates myocardial injury and dysfunction in a rat model of acute myocarditis. PG - 88-97 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 (3x10(6) 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. FAU - Ohnishi, Shunsuke AU - Ohnishi S AD - Department of Regenerative Medicine and Tissue Engineering, National Cardiovascular Center Research Institute, Fujishirodai 5-7-1, Osaka 565-8565, Japan. FAU - Yanagawa, Bobby AU - Yanagawa B FAU - Tanaka, Koichi AU - Tanaka K FAU - Miyahara, Yoshinori AU - Miyahara Y FAU - Obata, Hiroaki AU - Obata H FAU - Kataoka, Masaharu AU - Kataoka M FAU - Kodama, Makoto AU - Kodama M FAU - Ishibashi-Ueda, Hatsue AU - Ishibashi-Ueda H FAU - Kangawa, Kenji AU - Kangawa K FAU - Kitamura, Soichiro AU - Kitamura S FAU - Nagaya, Noritoshi AU - Nagaya N LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20061113 PL - England TA - J Mol Cell Cardiol JT - Journal of molecular and cellular cardiology JID - 0262322 RN - EC 2.7.3.2 (Creatine Kinase) SB - IM MH - Acute Disease MH - Animals MH - Apoptosis MH - Creatine Kinase/metabolism MH - Disease Models, Animal MH - In Vitro Techniques MH - Male MH - *Mesenchymal Stem Cell Transplantation MH - Myocarditis/pathology/physiopathology/*therapy MH - Myocytes, Cardiac/pathology MH - Neovascularization, Physiologic MH - Rats MH - Rats, Inbred Lew EDAT- 2006/11/15 09:00 MHDA- 2007/02/28 09:00 CRDT- 2006/11/15 09:00 PHST- 2006/05/11 00:00 [received] PHST- 2006/08/29 00:00 [revised] PHST- 2006/10/02 00:00 [accepted] PHST- 2006/11/15 09:00 [pubmed] PHST- 2007/02/28 09:00 [medline] PHST- 2006/11/15 09:00 [entrez] AID - S0022-2828(06)00959-X [pii] AID - 10.1016/j.yjmcc.2006.10.003 [doi] PST - ppublish SO - J Mol Cell Cardiol. 2007 Jan;42(1):88-97. doi: 10.1016/j.yjmcc.2006.10.003. Epub 2006 Nov 13.