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DOI: 10.1055/s-0032-1332453
What is the immunologic impact after transplantation of a novel fibrin-based type of engineered heart tissue?
Aims: Currently different cell-based treatment strategies for cardiac regeneration are pursued using diverse techniques of myocardial tissue engineering. The impact of immune responses to cellular or matrix components of transplanted engineered heart tissue (EHT) on graft survival remains 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 (NRHC) from Lewis rats were used to generate 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 immunocompromised 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 EHT revealed matrix-directed TH1-based rejection in group 1 without collateral impairment of cell survival. NRHC from transgenic Lewis rats ubiquitously expressing a luciferase marker gene (luc+) were used for longitudinal monitoring of transplanted luc+ EHT using in vivo bioluminescence imaging (BLI). Here, unimpaired cell survival was observed in syngeneic (group 1) and immunocompromised (group 3) recipients up to 110 days of follow-up. In an allogeneic setting (group 2), graft survival was limited to 14 ± 1 days post transplantation.
Conclusions: The 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 immunocompromised setting. Directed elimination of matrix material by antigen rejection may prove beneficial in that it selectively preserves transplanted cells in host myocardium.