Decellularization of Rat Aortic Valve Allografts Reduces the Cellular Immune Response Resulting in a Structurally Intact Collagen Network Irrespective of Collagen Denaturation

Background There is increasing evidence that the immunogenicity of aortic valve allografts (AVA) is associated with valvular degeneration. Chemically induced cell extraction is expected to reduce an immune response. However, whether this will translate into reduced structural damage is unclear. The present study focussed at characterizing the immune response to cellular and acellular AVA and correlation of results to structural damage. Material and Methods Rat aortic valve conduits were decellularized by a recently developed 2-step detergent-enzymatic extraction method. Cellular allogeneic (n = 8), acellular, allogeneic (n = 8), and syngeneic (n = 8) aortic valve conduits were grafted into the descending aorta for either 7 (n = 4) or 21 (n = 4) days. Immuno-histochemistry to detect lymphocyte and macrophage infi ltration (CD8 and CD68) and apoptosis, as well as histological and chemical analysis of collagen damage were performed. Results A severe infl ux of CD8+ and CD68+ cells accompanied by interstitial cell apoptosis was observed 1 week after AVA transplantation, followed by extensive fragmentation of the collagen matrix at 3 weeks. Decellularisation resulted in an absent cellular infi ltration with preservation of the collagen matrix. Chemical analysis revealed an increase in denatured collagen after decellularization (7.8 ± 0.7 % vs. 12.0 ± 1.2 %, p < 0.05), which did not change 3 weeks after transplantation (12.0 ± 1.8 %, p = ns), in contrast to the increase in cellular AVAs (12.3 ± 1.5 %, p < 0.05). Conclusion Transplantation of acellular AVA results in an absent early immune response, with a histological preservation of the valvular collagenous structure at 3 weeks. The amount of denatured collagen increases after decellularization, but does not increase further after transplantation, in contrast to cellular AVAs.