GW25-e4103 The experimental study on end-stage dilated cardiomyopathy by autotransplanting mesenchymal stem cells in swine

Abstract

Objectives: Cellular cardiomyoplasty has been proposed as an alternative strategy for augmenting the function of diseased myocardium. Many data have suggested that mesenchymal stem cells (MSC) may contribute to the healing of dilated cardiomyopathy. We will investigate whether autotransplantation with MSC can treat end-stage heart failure and its mechanism. Methods: Heart failure was created in 15 swines by right ventricular pacing-induced at the rate of 230 beats per minute for 4 weeks, and 190 beats per minute for another 4 weeks.Bone marrow aspirate was taken from the iliac crest of healthy swines. MSCs were isolated and co-cultured with 5-aza for 24hours. All the swines were divided into three groups: DMEM implantation group (DMEM); MSC implantation group (MSC); cardiomyocyte-like cell implantation group (CSC); The stem cells were injected into coronary artery of the porcines with heart failure under DSA. The ejection fraction (EF), the thickness of left ventricular wall, the diastolic diameter of left ventricle (LVDd) and CO were assessed by echocardiography before and 4 week after implantation.The TNF, TGF were detected with ELISA in the serum;the percentage of apotosis, the concentrtion of collagen and the ratio of collagen I/III were detected in the heart tissues. Results: A part of MSCs induced by 5-aza had morphological changes and 31 % stained positively Troponin I. Compared with that of the control group, LVEDd of implantation groups was smaller 4 weeks after stem cells implantation (P<0.05), whereas EF was increased (P<0.05). The TNF, the concentrtion of collagen and the percentage of apotosis decreased, whereas TGF, the ratio of collagen I/III increased in implantation groups vs control group. Conclusions: The MSCs can differentiate into cardiomyocytes by 5-aza in vitro.Autologous MSC transplantation improves contractibility of heart failure. This improvement might result from BMC-associated myocardial regeneration and neovascularization.This technique may lead to a promising therapy to treat congestive heart failure.