Effect of human umbilical cord mesenchymal stem cells transplantation on myocardial regeneration of mini-swine model with acute myocardial infarction

Objective To investigate the feasibility and mechanism of transplanted cells in the treatment of AMI and to detect the effects of epicardial multi-point injection in swine model of AMI on myocardial cell regeneration.Methods UC-MSCs were isolated from human umbilical cord in sterile conditions and expanded to the fifth generation.UC-MSCs were labeled with CM-Dil before transplantation.The 18 established AMI model miniswines were randomly divided into three groups,which were control group(n=6),PBS group(n=6) and transplantation group(n=6).PBS and UC-MSCs were injected into infarction area in PBS group and transplantation group,respectively.Six weeks later,evaluation of perfusion in infarction area was performed by SPECT in each group.The animals were euthanized and the tissues in infarction area were harvested to analyze the survival,proliferation and differentiation of stem cells as well as to observe the myocardial fibrosis,apoptosis and ventricular reconstruction.Results The perfusion was significantly improved in the transplantation group as compared with the control and PBS groups(P0.01).Immunofluorescence results confirmed that the transplanted UC-MSCs were still alive and part of them appeared to have differentiated into cardiomyocytes and vascular endothelium cells six weeks after transplantation.Meantime,it was also observed that resident CSCs differentiated into neonatal cardiomyocytes and vascular endotheliums.The TUNEL analysis indicated that the number of apoptosis was significantly reduced in the transplantation groups(P0.01).Masson staining confirmed that there were more viable myocardium and less fibrous tissue in the transplantation group(P0.01).Conclusions Transplantion of human UC-MSCs into infarction area of AMI was suit for the survival and differentiation of myocardial cell,as well as the promotion of CSCs recruitment and differentiation.In addition,UC-MSCs transplantation reduced myocardial cell apoptosis and fibrosis,enhanced viable myocardium and thus suppressed the ventricular reconstruction.