Abstract 9450: Allogeneic Fetal Membrane-Derived Mesenchymal Stem Cells Sheet Transplantation Therapy for Myocardial Infarction
Background: Bone marrow (BM) aspiration procedures are invasive and yield low numbers of mesenchymal stem cells (MSC) after processing, so we focused on fetal membranes (FMs) as an alternative source of MSC to provide a large number of cells. We previously reported allogeneic FM-derived MSC (FM-MSC) transplantation evaded rejection and provided significant improvement in a rat hind limb ischemia model. In this study, we investigated whether transplantation of allogeneic FM-MSC sheet could attenuate myocardial injury and dysfunction in a rat myocardial infarction (MI) model.
Methods and Results: FM-MSC were obtained from green fluorescent protein (GFP)-transgenic SD rats, and BM-MSC were obtained from GFP-transgenic Lewis rats. The monolayered MSC sheets were harvested from temperature-responsive dishes (3.3×106 cells per 35-mm dish) and were stacked to two layers. MI was induced in Lewis rats by coronary ligation. Allogeneic FM-MSC sheet or autologous BM-MSC sheet were transplanted onto the scarred myocardium 4 week after ligation. At 1 day and 4 weeks after transplantation, both GFP-positive MSC were engrafted in the heart. At 4 weeks after transplantation, allogeneic FM-MSC sheet transplantation significantly reversed wall thinning in the scar area and improved cardiac function compared with the control group [ejection fraction (EF); 55.4 ± 2.6 vs. 44.0 ± 3.2%, respectively, n=10, P<0.05], comparable to autologous BM-MSC sheet transplantation (EF; 56.3 ± 2.4%, n=10, P<0.05 vs. the control group) in rats with MI. Furthermore, the infarcted regional capillary density was increased (216.2 ± 15.8 vs. 151.8 ± 16.6 vessels/mm2, P<0.05 vs. the control group) and the fibrosis area was decreased in the FM-MSC sheet transplanted group as well as the BM-MSC sheet transplanted group (capillary density; 206.2 ± 11.5 vessels/mm2, P<0.05 vs. the control group).
Conclusions: Simillar to autologous BM-MSC, allogeneic FM-MSC sheet transplantation attenuated myocardial dysfunction, wall thinning and fibrosis in a rat model of MI. FMs are generally treated as medical waste and that MSC can be obtained abundantly without invasive procedures. Thus, allogeneic FM-MSC sheet transplantation might be a new therapeutic strategy for the treatment of MI.
- © 2010 by American Heart Association, Inc.