Decellularization of xenogeneic heart valves might lead to excellent regenerative implants,from which many patients could benefit.However,this material carries various xenogeneic epitopes and thus bears a considerable...Decellularization of xenogeneic heart valves might lead to excellent regenerative implants,from which many patients could benefit.However,this material carries various xenogeneic epitopes and thus bears a considerable inherent immunological risk.Here,we investigated the regenerative and immunogenic potential of xenogeneic decellularized heart valve implants using pigs deficient for the galactosyltransferase gene(GGTA1-KO)as novel large animal model.Decellularized aortic and pulmonary heart valves obtained from sheep,wild-type pigs or GGTA1-KO pigs were implanted into GGTA1-KO pigs for 3,or 6 months,respectively.Explants were analyzed histologically,immunhistologically(CD3,CD21 and CD172a)and anti-aGal antibody serum titers were determined by ELISA.Xenogeneic sheep derived implants exhibited a strong immune reaction upon implantation into GGTA1-KO pigs,characterized by massive inflammatory cells infiltrates,presence of foreign body giant cells,a dramatic increase of anti-aGal antibody titers and ultimately destruction of the graft,whereas wild-type porcine grafts induced only a mild reaction in GGTA1-KO pigs.Allogeneic implants,wild-type/wild-type and GGTA1-KO/GGTA1-KO valves did not induce a measurable immune reaction.Thus,GGTA1-KO pigs developed a‘human-like’immune response toward decellularized xenogeneic implants showing that immunogenicity of xenogeneic implants is not sufficiently reduced by decellularization,which detracts from their regenerative potential.展开更多
基金the Fordergemeinschaft Deutsche Kinderherzzentren e.V.,the Deutsche Herzstiftung e.V.,and the German Research Foundation DFG via the Cluster of Excellence‘From regenerative biology to reconstructive therapy’(REBIRTH)and via projects B1 and C7 of TRR127(Biology of xenogeneic cell and organ transplantation-from bench to bedside).
文摘Decellularization of xenogeneic heart valves might lead to excellent regenerative implants,from which many patients could benefit.However,this material carries various xenogeneic epitopes and thus bears a considerable inherent immunological risk.Here,we investigated the regenerative and immunogenic potential of xenogeneic decellularized heart valve implants using pigs deficient for the galactosyltransferase gene(GGTA1-KO)as novel large animal model.Decellularized aortic and pulmonary heart valves obtained from sheep,wild-type pigs or GGTA1-KO pigs were implanted into GGTA1-KO pigs for 3,or 6 months,respectively.Explants were analyzed histologically,immunhistologically(CD3,CD21 and CD172a)and anti-aGal antibody serum titers were determined by ELISA.Xenogeneic sheep derived implants exhibited a strong immune reaction upon implantation into GGTA1-KO pigs,characterized by massive inflammatory cells infiltrates,presence of foreign body giant cells,a dramatic increase of anti-aGal antibody titers and ultimately destruction of the graft,whereas wild-type porcine grafts induced only a mild reaction in GGTA1-KO pigs.Allogeneic implants,wild-type/wild-type and GGTA1-KO/GGTA1-KO valves did not induce a measurable immune reaction.Thus,GGTA1-KO pigs developed a‘human-like’immune response toward decellularized xenogeneic implants showing that immunogenicity of xenogeneic implants is not sufficiently reduced by decellularization,which detracts from their regenerative potential.
