Abstract 421: Injection Of Self-assembled Nanopeptides With Clonal Cardiac Sca-1 Positive Cells Improve Cardiac Function After Myocardial Infarction
Biological scaffolds have been reported to offer microenvironment for the transplanted cells, support the cell survival and maintain the release of paracrine factors. However, it is still unknown what kinds of cell sources, scaffolds and their delivery methods are suitable for myocardial repair. Self-assembled nanopeptides, Puramatrix (PM), have been reported to be superior to the other scaffolds in terms of its animal free origin, biodegradability and non-immunogenic properties, which are prerequisite for the clinical application. To examine whether cell transplantation with PM can restore the cardiac function of C57BL/6 mouse myocardial infarction (MI) models, we injected the cell-PM complex into the peri-MI area and then overlay a thick hydrogel patch on the MI area. The mice were divided into following groups according to the transplanted cell types and matrices; bone marrow mononuclear cells with PM (BM/PM), clonal Sca-1 positive cardiac progenitors with PM (cSca-1/PM) and PM alone (PM). Non-treated MI models (Cont) were prepared as controls. Infarct area was examined by Masson trichrome staining and cardiac dimension and function were examined by echocardiography two weeks after transplantation. cSca-1/PM and PM attenuated ventricular enlargement in comparison with BM/PM and Cont (left ventricular diastolic dimension: cSca-1/PM 4.9 ± 0.6 mm, PM 5.3 ± 1.0 mm, BM/PM 6.6 ± 0.1 mm, Cont 6.1 ± 0.1 mm). Fractional shortening of cSca-1/PM and PM were higher than that of BM/PM and Cont (cSca-1/PM 14 ± 3.2%, PM 13 ± 2.3%, BM/PM 8.0 ± 2.5%, Cont 9.9 ± 3%). Infarct area of cSca-1/PM was smaller than that of BM/PM, PM and Cont (cSca-1/PM 36 ± 12%, BM/PM 50 ± 3.1%, PM 53 ± 18%, Cont 57 ± 4.0%). To elucidate the mechanisms of the beneficial effects of cSca-1/PM complex on the infarct area, the number of CD31 positive capillary was examined by immunohistochemical method. Capillary density in the infarct area of cSca-1/PM was higher than that of PM (cSca-1/PM 15%, PM 8%). In summary, transplantation of cSca-1 in combination with PM prevents cardiac remodeling, improves cardiac contraction and reduces infarct area partially through angiogenesis. Cell therapy with PM may enable us to circumvent the current problem in the efficiency of tissue engineering-based cell therapy.