Effects of transplantation of autologous adipose-derived stem cells versus bone marrow mononuclear cells on the treatment of myocardial infarction

Background: It is a debate of bone marrow mononuclear cells to promote the regeneration of infarcted myocardium. Previous studies believed that it was effective, and even bone marrow mononuclear cells could differentiate into cardiomyocytes. But, present articles denied this opinion and confirmed that mononuclear cells only can limitedly enhance angiogenesis. Objective: To compare the efficacy of autologous transplantation of adipose-derived stem cells (ASCs) and bone marrow mononuclear cells in treatment of cardiomyocyte regeneration, angiogenesis and heart function after myocardial infarction. Design, time and setting: The randomized control animal experiment was performed at the Laboratory of Department of Cardiology, General Hospital of Chinese PLA and Laboratory of General Hospital of Shenyang Military Area Command of Chinese PLA from January 2004 to September 2005. Materials: Fifty-five clean 4-months old male New Zealand rabbits were used in the study. Ten were used for tracing bone marrow mononuclear cells. The remaining was randomly assigned into ASC group, bone marrow mononuclear cell group and blank control group, with 15 in each group. Methods: Rabbit models of myocardial infarction were established by ligating anterior descending coronary artery in each group. During model induction, a little abdominal adipose tissue was used to harvest ASCs, and bone marrow of iliac bone was employed to collect bone marrow mononuclear cells for autologous transplantation. Three weeks later, autologous ASCs and bone marrow mononuclear cells were respectively directly injected into infarcted myocardium in the ASC group and bone marrow mononuclear cell group. Phosphate buffer saline was injected into the blank control group. Five weeks after cell transplantation, ten rabbits were labeled with DAPI and BrdU. Transplanted cells received BrdU labeling in the ASC group. Main outcome measures: Transplanted cell labeling; Heart function changes after transplantation; Results of Hematoxylin & Eosin (HE) staining and immunohistochemistry. Results: In the ASC group, transplanted cells were detected in infarcted region, which could differentiate into cardiomyocytes, endothelial cells and participated in neovascularization. In the bone marrow mononuclear cell group, mononuclear cells were not measured in the infarcted myocardium after DAPI and BrdU labeling. Before cell transplantation, there was no significant difference in cardiac function among three groups. Five weeks after cell transplantation, echocardiography and left ventricular pressure tracing demonstrated that the cardiac function significantly improved in ASC group compared with blank control group (P < 0.05). However, the cardiac function in bone marrow mononuclear cell group was almost the same as control except +dp/dtmax (P < 0.05). The capillary density in both ASC and bone marrow mononuclear cell groups was greater than that in blank control group (P < 0.01, P < 0.05). Many blood vessels were observed both in the middle of and at the border of the infarction region in ASC group, while in bone marrow mononuclear cell group, the blood vessels could only found at the infarction border. Conclusion: Transplantation of ASCs is a useful strategy for therapeutic cardiomyogenesis and neovascularization, resulting in amelioration of cardiac function. Although transplantation of bone marrow mononuclear cells can promote angiogenesis, its efficacy in amelioration of cardiac function is limited.