Effects of mesenchymal stem cell transplantation on extracellular matrix after myocardial infarction in rats

Objective The present study was to determine the effects of mesenchymal stem cell (MSC) transplantation into ischemic myocardium on left ventricular (LV) function and remodeling, especially the changes in extracellular matrix (ECM) and in transforming growth factor (TGF)-beta(1) after myocardial infarction (MI). Methods In this study, we investigated the changes in ECM involving collagen type 1, collagen type III, matrix metalloproteinase (MMP)-1, tissue inhibitor of matrix metalloproteinase (TIMP)-1 and in TGF-beta(1), mRNA expressions by using reverse transcription-polymerase chain reaction (RT-PCR) and in situ hybridization after MSC transplantation into infarcted myocardium in rats. Protein expressions were detected by immunohistochemistry and western blot. Seven and 28 days after coronary artery ligation, hemodynamic evaluations were performed. Results Heart: body weight ratio in the MI + MSC group decreased after MSC transplantation into infarcted myocardium compared with the MI group. However, LV systolic pressure (LVSP) and LV peak velocities of contraction and relaxation (+dP/dt(max) and -dP/dt(max)) significantly increased compared with the MI group (P < 0.01). There was marked up-regulation of mRNA transcription for ECM and TGF-beta(1) proteins in MI rats. Immunohistochemical and western blot studies confirmed that the expressions of these ECM and TGF-beta(1) proteins were significantly increased in the MI group. The mRNA and protein expressions of collagen type 1, Collagen type III, TIMP-1 and TGF-beta(1), were all decreased by MSC transplantation in our study, although no significant difference was found for the mRNA and protein expressions of MMP-1 between the MI group and the MI + MSC group. Conclusions Our results demonstrated that MSC transplantation could inhibit LV remodeling and improve heart function. (c) 2005 Lippincott Williams & Wilkins.