{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,6]],"date-time":"2026-04-06T21:03:04Z","timestamp":1775509384130,"version":"3.50.1"},"reference-count":33,"publisher":"Oxford University Press (OUP)","issue":"5","funder":[{"name":"Deutsche Herzstiftung e. V."},{"DOI":"10.13039\/501100001659","name":"German Research Foundation","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,8,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>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\u2009months, respectively. Explants were analyzed histologically, immunhistologically (CD3, CD21 and CD172a) and anti-\u03b1Gal 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-\u03b1Gal 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 \u2018human-like\u2019 immune response toward decellularized xenogeneic implants showing that immunogenicity of xenogeneic implants is not sufficiently reduced by decellularization, which detracts from their regenerative potential.<\/jats:p>","DOI":"10.1093\/rb\/rbab036","type":"journal-article","created":{"date-parts":[[2021,8,3]],"date-time":"2021-08-03T06:01:54Z","timestamp":1627970514000},"source":"Crossref","is-referenced-by-count":20,"title":["Immunological and functional features of decellularized xenogeneic heart valves after transplantation into GGTA1-KO pigs"],"prefix":"10.1093","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8556-116X","authenticated-orcid":false,"given":"Robert","family":"Ramm","sequence":"first","affiliation":[{"name":"Leibniz Research Laboratories for Biotechnology and Artificial Organs (LEBAO), Hannover Medical School, Carl-Neuberg Str. 1, Hannover 30625, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tobias","family":"Goecke","sequence":"additional","affiliation":[{"name":"Leibniz Research Laboratories for Biotechnology and Artificial Organs (LEBAO), Hannover Medical School, Carl-Neuberg Str. 1, Hannover 30625, Germany"},{"name":"Department of Cardiac-, Thoracic-, Transplantation and Vascular Surgery, Hannover Medical School, Carl-Neuberg Str. 1, Hannover 30625, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peter","family":"K\u00f6hler","sequence":"additional","affiliation":[{"name":"Institute of Farm Animal Genetics, Friedrich-Loeffler-Institut, Hoeltystr. 10, 31535 Mariensee\/Neustadt am Ruebenberge, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Igor","family":"Tudorache","sequence":"additional","affiliation":[{"name":"Department of Cardiac-, Thoracic-, Transplantation and Vascular Surgery, Hannover Medical School, Carl-Neuberg Str. 1, Hannover 30625, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Serghei","family":"Cebotari","sequence":"additional","affiliation":[{"name":"Department of Cardiac-, Thoracic-, Transplantation and Vascular Surgery, Hannover Medical School, Carl-Neuberg Str. 1, Hannover 30625, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anatol","family":"Ciubotaru","sequence":"additional","affiliation":[{"name":"Department of Cardiac-, Thoracic-, Transplantation and Vascular Surgery, Hannover Medical School, Carl-Neuberg Str. 1, Hannover 30625, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7277-7597","authenticated-orcid":false,"given":"Samir","family":"Sarikouch","sequence":"additional","affiliation":[{"name":"Department of Cardiac-, Thoracic-, Transplantation and Vascular Surgery, Hannover Medical School, Carl-Neuberg Str. 1, Hannover 30625, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Klaus","family":"H\u00f6ffler","sequence":"additional","affiliation":[{"name":"Department of Cardiac-, Thoracic-, Transplantation and Vascular Surgery, Hannover Medical School, Carl-Neuberg Str. 1, Hannover 30625, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Friederike","family":"Bothe","sequence":"additional","affiliation":[{"name":"Medimplant GmbH, Bischofsholer Damm 15, Hannover 30173, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bj\u00f6rn","family":"Petersen","sequence":"additional","affiliation":[{"name":"Institute of Farm Animal Genetics, Friedrich-Loeffler-Institut, Hoeltystr. 10, 31535 Mariensee\/Neustadt am Ruebenberge, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Axel","family":"Haverich","sequence":"additional","affiliation":[{"name":"Leibniz Research Laboratories for Biotechnology and Artificial Organs (LEBAO), Hannover Medical School, Carl-Neuberg Str. 1, Hannover 30625, Germany"},{"name":"Department of Cardiac-, Thoracic-, Transplantation and Vascular Surgery, Hannover Medical School, Carl-Neuberg Str. 1, Hannover 30625, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Heiner","family":"Niemann","sequence":"additional","affiliation":[{"name":"Institute of Farm Animal Genetics, Friedrich-Loeffler-Institut, Hoeltystr. 10, 31535 Mariensee\/Neustadt am Ruebenberge, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7123-2410","authenticated-orcid":false,"given":"Andres","family":"Hilfiker","sequence":"additional","affiliation":[{"name":"Leibniz Research Laboratories for Biotechnology and Artificial Organs (LEBAO), Hannover Medical School, Carl-Neuberg Str. 1, Hannover 30625, Germany"},{"name":"Department of Cardiac-, Thoracic-, Transplantation and Vascular Surgery, Hannover Medical School, Carl-Neuberg Str. 1, Hannover 30625, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2021,8,3]]},"reference":[{"key":"2021080908321304200_rbab036-B1","doi-asserted-by":"crossref","first-page":"430","DOI":"10.1038\/s41586-018-0765-z","article-title":"Consistent success in life-supporting porcine cardiac xenotransplantation","volume":"564","author":"Langin","year":"2018","journal-title":"Nature"},{"key":"2021080908321304200_rbab036-B2","doi-asserted-by":"crossref","first-page":"2531","DOI":"10.1111\/ajt.14311","article-title":"The resurgence of xenotransplantation","volume":"17","author":"Cowan","year":"2017","journal-title":"Am J Transplant"},{"key":"2021080908321304200_rbab036-B3","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1038\/nbt0116-3","article-title":"Xenotransplantation makes a comeback","volume":"34","author":"Perkel","year":"2016","journal-title":"Nat 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