Abstract 11908: Assessment of Immunobiology of Fibrin-based Engineered Heart Tissue
Objectives Currently different cell-based treatment strategies for cardiac regeneration are pursued using diverse techniques of myocardial tissue engineering. To date, impact of immune responses to cellular or matrix components of transplanted engineered heart tissue (EHT) on graft survival are widely unclear. The aim of this study was to assess immune responses after transplantation of a novel type of fibrin-based EHT and to monitor graft survival under different immunologic conditions.
Methods/Results Neonatal rat heart cells from transgenic Lewis rats ubiquitously expressing a luciferase marker gene (luc+) were used to generate luc+ fibrin-based EHT. Three-dimensional, spontaneously and coherently contracting EHT constructs were transplanted onto the left-ventricular myocardium of syngeneic Lewis (group 1, n=6), allogeneic Brown Norway (group 2, n=6), or immunodeficient RNU rats (group 3, n=6). After EHT transplantation, systemic activation of immune cells was observed in group 1 and 2 (49±37 and 43±31 spot frequency respectively, p=ns), while no immune response was observed in group 3 as expected (10±5 spot frequency, p<0.001 versus groups 1 and 2). Local CD3- and CD68-positive cell infiltration was observed in groups 1 and 2. Further detailed analysis differentiating immune responses against cellular and matrix components of luc+ EHT revealed matrix-directed TH1-based rejection in group 1 without collateral impairment of cell survival. Longitudinal monitoring of transplanted luc+ EHT using in vivo bioluminescence imaging revealed unimpaired cell survival in syngeneic (group 1) and immunodeficient (group 3) recipients up to 120 days of follow-up. In an allogeneic setting (group 2), graft survival was limited to 14±1 days post transplantation.
Conclusions The present study demonstrates that EHT with autologous cell content may be a promising approach for regeneration of dysfunctional myocardium. Despite rejection of matrix components, cell survival was equivalent in the syngeneic compared to the immunodeficient setting. Directed elimination of matrix material by antigen rejection may prove beneficial in that it selectively preserves transplanted cells in host myocardium.
- © 2012 by American Heart Association, Inc.