Cell engraftment, differentiation and contribution to cardiac function recovery of umbilical cord derived mesenchymal stem cells

Objective To investigate the survival and engraftment of human umbilical cord derived mesenchymal stem cells (UC-MSCs) and its contribution to cardiac functional recovery in a rat myocardial infarction(MI) model. Methods From October 2010 to June 2011, 10 human umbilical cord tissues were obtained from Obstetrics and Gynecology Department, Nanjing Gulou Hospital. The UC-MSCs were isolated by enzyme digestion. Thirty old male SD rats (8-week, weight 260-280 g) were used to establish MI model by high ligation of left anterior descending coronary artery. Fourteen days after induction of MI, echocardiography was used to assess the cardiac function, and the successfully established MI rats were randomly divided into cell transplantation group and phosphate buffered saline (PBS) control group. Cardiac function was assessed by echocardiography pre-transplantation, 14 and 28 days after cell transplantation. At day 30, the rats were sacrificed to make heart tissue frozen sections. Vascular smooth muscle actin (α-SMA), von Willebrand factor (vWF), and cardial troponin-T (cTnT) staining were performed and immunofluorescence was used to investigate the survival, engraftment and differentiation of transplanted cells. Results Twenty-three MI rats were successfully established in 30 rats, and 20 rats survived after cell transplantation, 10 in transplantation group and 10 in control group. By echocardiography, compared with pre-transplantation, the improvement of left ventricular ejection fraction (LVEF) and left ventricular fractional shortening (LVFS) were observed, and the differences were statistically significant (tLVEF=3.864, 3.690, tLVFS=6.397, 5.904, all P values 0.05) but LVFS was significantly higher in transplantation group (t=2.771, P<0.05). At day 28, both LVEF and LVFS were better in transplantation group (t=2.977, 2.140, all P values<0.05). Immunofluorescence revealed that the transplanted UC-MSCs survived and engrafted in the infarted myocardium and α-SMA, vWF, and cTnT staining showed that transplanted UC-MSCs differentiated into smooth muscle cells, endothelial cells, and cardiomyocytes. Conclusions UC-MSCs can engraft the infarcted myocardium and have the ability to differentiate into smooth muscle, endothelial, and cardiomyocytic cells in the local MI environment, contribute to myocardial regeneration, angiogenesis and the cardiac functional recovery. Key words: Cord blood stem cell transplantation; Cell differentiation; Myocardial infarction; Models, animal; Rats