Kasimir Marie-Theres, Rieder Erwin, Seebacher Gernot, Wolner Ernst, Weigel Guenter, Simon Paul
Department of Cardiothoracic Surgery, Medical University of Vienna, Austria.
Tissue Eng. 2005 Jul-Aug;11(7-8):1274-80. doi: 10.1089/ten.2005.11.1274.
Tissue engineering of heart valves promises to create functional autologous tissue with the potential for regeneration and growth without the limitations of current heart valve prostheses. The appropriate valve matrix is essential. Porcine heart valves are attractive because of their anatomical similarity. Decellularization is used for antigen reduction. The efficacy of published protocols varies, however. The absence of a specific immunological or unspecific inflammatory reaction is mandatory. The porcine cell-specific alpha-Gal epitope is known to be responsible for hyperacute rejection in xenotransplantation. In tissue engineering residual alpha-Gal epitope may induce severe inflammation in humans and may lead to graft failure. In this study porcine pulmonary conduits were decellularized with Triton X-100, sodium deoxycholate, Igepal CA-630, and ribonuclease treatment and were compared with specimens of the commercially available porcine decellularized SynerGraft regarding cell removal and elimination of the alpha-Gal epitope. In addition, samples of a porcine bioprosthesis were examined for the presence of the alpha-Gal epitope. In conclusion, we describe for the first time the presence of the alpha-Gal epitope in clinically used porcine bioprostheses and the first generation of a commercial tissue-engineered heart valve. In contrast, complete cell and alpha-Gal removal was achieved by a decellularization procedure developed by our group.
心脏瓣膜组织工程有望制造出具有再生和生长潜力的功能性自体组织,而不受当前心脏瓣膜假体的限制。合适的瓣膜基质至关重要。猪心脏瓣膜因其解剖学相似性而颇具吸引力。去细胞化用于减少抗原。然而,已发表方案的效果各不相同。必须不存在特异性免疫反应或非特异性炎症反应。已知猪细胞特异性α-Gal表位是异种移植中超急性排斥反应的原因。在组织工程中,残留的α-Gal表位可能会在人体内引发严重炎症,并可能导致移植物失败。在本研究中,用Triton X-100、脱氧胆酸钠、Igepal CA-630和核糖核酸酶处理对猪肺动脉导管进行去细胞化,并与市售的去细胞猪SynerGraft标本在细胞去除和α-Gal表位消除方面进行比较。此外,还检查了猪生物假体样本中α-Gal表位的存在情况。总之,我们首次描述了临床使用的猪生物假体和第一代商业组织工程心脏瓣膜中α-Gal表位的存在情况。相比之下,我们团队开发的去细胞化程序实现了完全去除细胞和α-Gal。