Abstract: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).Group comparison: at day 14, there was no difference in LVEF (P>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.
武开宏,孙剑,莫绪明. 人脐带干细胞移植在心肌梗死大鼠心肌内的迁移、分化及对心脏功能的影响[J]. 中华解剖与临床杂志, 2016, 21(5): 469-473.
Wu Kaihong, Sun Jian, Mo Xuming.. Cell engraftment, differentiation and contribution to cardiac function recovery of umbilical cord derived mesenchymal stem cells. Chinese Journal of Anatomy and Clinics, 2016, 21(5): 469-473.
Kim PJ, Mahmoudi M, Ge X, et al. Direct evaluation of myocardial viability and stem cell engraftment demonstrates salvage of the injured myocardium[J]. Circ Res, 2015, 116(7): e40-e50. DOI:10.1161/CIRCRESAHA.116.304668
[2]
Zhang H, Wang H, Li N, et al. Cardiac progenitor/stem cells on myocardial infarction or ischemic heart disease: what we have known from current research[J]. Heart Fail Rev, 2014, 19(2): 247-258. DOI:10.1007/s10741-013-9372-0
Goumans MJ, Maring JA, Smits AM. A straightforward guide to the basic science behind cardiovascular cell-based therapies[J]. Heart, 2014, 100(15): 1153-1157. DOI:10.1136/heartjnl-2014-305646
[7]
Rodrigo SF, van Ramshorst J, Hoogslag GE, et al. Intramyocardial injection of autologous bone marrow-derived ex vivo expanded mesenchymal stem cells in acute myocardial infarction patients is feasible and safe up to 5 years of follow-up[J]. J Cardiovasc Transl Res, 2013, 6(5): 816-825. DOI:10.1007/s12265-013-9507-7
[8]
Zhao JJ, Liu XC, Kong F, et al. Bone marrow mesenchymal stem cells improve myocardial function in a swine model of acute myocardial infarction[J]. Mol Med Rep, 2014, 10(3): 1448-1454. DOI:10.3892/mmr.2014.2378