rada16-i and Myocardial-Infarction

Topics: Animals; Cell Survival; Coated Materials, Biocompatible; Disease Models, Animal; Heart Failure; Heart Function Tests; Hydrogel, Polyethylene Glycol Dimethacrylate; Hydrogen-Ion Concentration; Male; Mesenchymal Stem Cell Transplantation; Mesenchymal Stem Cells; Myocardial Infarction; Peptides; Pericardium; Rats, Inbred Lew; Rats, Sprague-Dawley

Progress in stem cell transplantation for the treatment of myocardial infarction is hampered by the poor retention and survival of the implanted cells. To enhance cell survival and differentiation and thereby improve the efficiency of stem cell therapy, we constructed a novel self-assembling peptide by attaching an RGDSP cell-adhesion motif to the self-assembling peptide RADA16. c-kit(pos)/Nkx2.5(low)/GATA4(low) marrow-derived cardiac stem cells (MCSCs), which have a specific potential to differentiate into cardiomyocytes, were isolated from rat bone marrow. The cytoprotective effects of RGDSP scaffolds were assessed by exposure of MCSCs to anoxia in vitro. The efficacy of transplanting MCSCs in RGDSP scaffolds was evaluated in a female rat MI model. The designer self-assembling peptide self-assembled into RGDSP nanofiber scaffolds under physiological conditions. RGDSP scaffolds were beneficial for the growth of MCSCs and protected them from apoptosis and necrosis caused by anoxia. In a rat MI model, cardiac function was improved and collagen deposition was markedly reduced in the group receiving MCSCs in RGDSP scaffolds compared with groups receiving MCSCs alone, RGDSP scaffolds alone or MCSCs in RADA16 scaffolds. There were more surviving MCSCs in the group receiving MCSCs in RGDSP scaffolds than in the groups receiving MCSCs alone or MCSCs in RADA16 scaffolds. Most of the Y chromosome-positive cells expressed cardiac troponin T and connexin43 (Cx-43). These results suggest that RGDSP scaffolds provide a suitable microenvironment for the survival and differentiation of MCSCs. RGDSP scaffolds enhanced the efficacy of MCSC transplantation to repair myocardium and improve cardiac function.

Topics: Animals; Bone Marrow Cells; Bone Marrow Transplantation; Cell Culture Techniques; Cell Differentiation; Cell Survival; Fibrosis; Male; Myocardial Contraction; Myocardial Infarction; Myocytes, Cardiac; Nanofibers; Oligopeptides; Peptides; Rats; Rats, Sprague-Dawley; Stem Cell Transplantation; Ventricular Function, Left

Implantation of various types of cells into the heart has been reported to be effective for heart failure, however, it is unknown what kinds of cells are most suitable for myocardial repair. To examine which types of cells are most effective, we injected cell-Puramatrix™ (PM) complex into the border area and overlaid the cell-PM patch on the myocardial infarction (MI) area. We compared cardiac morphology and function at 2 weeks after transplantation. Among clonal stem cell antigen-1 positive cardiac progenitors with PM (cSca-1/PM), bone marrow mononuclear cells with PM (BM/PM), skeletal myoblasts with PM (SM/PM), adipose tissue-derived mesenchymal cells with PM (AMC/PM), PM alone (PM), and non-treated MI group (MI), the infarct area of cSca-1/PM was smaller than that of BM/PM, SM/PM, PM and MI. cSca-1/PM and AMC/PM attenuated ventricular enlargement and restored cardiac function in comparison with MI. Capillary density in the infarct area of cSca-1/PM was higher than that of other five groups. The percentage of TUNEL positive cardiomyocytes in the infarct area of cSca-1/PM was lower than that of MI and PM. cSca-1 secreted VEGF and some of them differentiated into cardiomyocytes and vascular smooth muscle cells. These results suggest that transplantation of cSca-1/PM most effectively prevents cardiac remodeling and dysfunction through angiogenesis, inhibition of apoptosis and myocardial regeneration.

Topics: Actins; Angiogenesis Inducing Agents; Animals; Antigens, Ly; Apoptosis; Capillaries; Cell Line; Cell Transdifferentiation; Heart Function Tests; Membrane Proteins; Mice; Myocardial Infarction; Myocardium; Myocytes, Cardiac; Myocytes, Smooth Muscle; Peptides; Stem Cell Transplantation; Stem Cells; Systole; Ultrasonography; Ventricular Remodeling; von Willebrand Factor