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Immunological and functional features of decellularized xenogeneic heart valves after transplantation into GGTA1-ko pigs

引用

Regenerative Biomaterials 2021年第5期8卷 25-36页

作者： Robert Ramm Tobias Goecke Peter kohler Igor Tudorache Serghei Cebotari Anatol Ciubotaru Samir Sarikouch Klaus Hoffler Friederike Bothe Bjorn Petersen Axel Haverich Heiner Niemann Andres Hilfiker Leibniz Research Laboratories for Biotechnology and Artificial Organs(LEBAO) Hannover Medical SchoolCarl-Neuberg Str.1Hannover 30625Germany Department of Cardiac- Thoracic-Transplantation and Vascular SurgeryHannover Medical SchoolCarl-Neuberg Str.1Hannover 30625Germany Institute of Farm Animal Genetics Friedrich-Loeffler-InstitutHoeltystr.1031535 Mariensee/Neustadt am RuebenbergeGermany Medimplant GmbH Bischofsholer Damm 15Hannover 30173Germany

Decellularization of xenogeneic heart valves might lead to excellent regenerative implants,from which many patients could ***,this material carries various xenogeneic epitopes and thus bears a considerable inherent immunological ***,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 *** 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,*** were analyzed histologically,immunhistologically(CD3,CD21 and CD172a)and anti-agal antibody serum titers were determined by *** 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 *** implants,wild-type/wild-type and GGTA1-ko/GGTA1-ko valves did not induce a measurable immune ***,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.

关键词： agal-ko pig decellularization heart valves xenoantibodies large animal model

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