Tissue implantation with autologous myoblast sheet improved cardiac performance in the impaired myocardium

Abstract

The transplantation of autologous skeletal myoblasts (SM) using direct injection has been applied clinically. Loss of transplanted Cells and ECM due to direct injection limits SM’s number and potential. As for the clinical trial using autologous cell source, autologous myoblasts is a candidate. We hypothesized that tissue implantation rather than cell transplantation might be more advantageous to regenerate the impaired heart. The impaired heart was created in twenty eight rats by ligating LAD for 2 weeks. Polymers (N-isopropylacrylamide), a temperature responsive domain, were coated on culture dish. SM’s isolated from leg muscle were cultured and detached from the dishes as single monolayer cell-sheet at 20° C. Following therapies were conducted: Two myoblast sheets implantation (S group = 107 cells); Cell inject (I group = 107 cells); Non-cellular therapy (C group = collagen sheet). Two weeks after, the cell sheets showed attachment to myocardium and migration of the SM to the scar area. Histology in S-group revealed greater cellularity without scar formation, abundant widespread neo-capillaries and reduction of LV dilatation due to significant uniform thickened wall (S-group = 1168 ± 436μm vs I-group = 732 ± 204μm vs C-group = 696.9 ± 3.41μm) while I-group only showed small patches of grafted myoblasts with dispersed neo-capillaries and without significant reduction in LV dilatation. Eight week after, cardiac performance remained significantly improved in S-group. I group also showed recovery in cardiac performance but not as significant as showed by S-group. Technical loss of delivered cells was lesser in S-group as compared with I-group at 15 mins and 1 day as analyzed by RT-PCR for the presence of Y-chromosome. SM-sheet implantation improved global cardiac function by attenuating the cardiac remodeling and regenerating the impaired myocardium as compared to cell transplantation, suggesting a promising strategy for myocardial regeneration therapy.