{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T20:37:22Z","timestamp":1791664642986,"version":"4.3.4"},"reference-count":19,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2022,9,20]],"date-time":"2022-09-20T00:00:00Z","timestamp":1663632000000},"content-version":"vor","delay-in-days":19,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Xenotransplantation"],"published-print":{"date-parts":[[2022,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>We have been testing genetically engineered (GE) pig hearts and optimizing immunosuppression (IS) in non\u2010human primates (NHPs) since 2005. We demonstrate how we translated this preclinical investigation into a US Food and Drug Administration (FDA)\u2010approved clinical cardiac xenotransplantation. First, genetically engineered (GE) pig hearts were transplanted into the abdomen of NHP along with IS, which included anti\u2010CD20 and anti\u2010CD40\u2010based co\u2010stimulation blockade antibodies. We reported 945 days of survival of three gene GE pig hearts in NHPs. Building on this proof\u2010of\u2010concept, we tested 3\u201310 gene\u2010modified GE pig hearts (in order to improve the immunocompatibility of the xenograft further) in a life\u2010supporting orthotopic model, but had limited success due to perioperative cardiac xenograft dysfunction (PCXD). With novel non\u2010ischemic continuous perfusion preservation (NICP), using the XVIVO Heart solution (XHS), life\u2010supporting survival was extended to 9 months. We approached the FDA under an application for \u201cExpanded Access\u201d (EA), to transplant a GE pig heart in a patient with end\u2010stage non\u2010ischemic cardiomyopathy. He was without other therapeutic options and dependent on VA\u2010ECMO. A team of FDA reviewers reviewed our preclinical research experience and data and allowed us to proceed. This clinical cardiac xenotransplantation was performed, and the patient survived for 60 days, demonstrating the translational preclinical investigation of cardiac xenotransplantation from bench to bedside. The ultimate etiology of graft failure is currently a topic of investigation and lessons learned will progress the field forward.<\/jats:p>","DOI":"10.1111\/xen.12776","type":"journal-article","created":{"date-parts":[[2022,9,20]],"date-time":"2022-09-20T11:54:38Z","timestamp":1663674878000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["The road to the first FDA\u2010approved genetically engineered pig heart transplantation into human"],"prefix":"10.1111","volume":"29","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8701-2260","authenticated-orcid":false,"given":"Avneesh K.","family":"Singh","sequence":"first","affiliation":[{"name":"University of Maryland School of Medicine Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bartley P.","family":"Griffith","sequence":"additional","affiliation":[{"name":"University of Maryland School of Medicine Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Corbin E.","family":"Goerlich","sequence":"additional","affiliation":[{"name":"University of Maryland School of Medicine Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Ayares","sequence":"additional","affiliation":[{"name":"Revivicor Inc Blacksburg Virginia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4654-783X","authenticated-orcid":false,"given":"Muhammad M.","family":"Mohiuddin","sequence":"additional","affiliation":[{"name":"University of Maryland School of Medicine Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,9,20]]},"reference":[{"key":"e_1_2_4_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm1171"},{"key":"e_1_2_4_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-6143.2011.03846.x"},{"key":"e_1_2_4_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/72162"},{"key":"e_1_2_4_5_1","doi-asserted-by":"publisher","DOI":"10.1097\/00007890-200208150-00024"},{"key":"e_1_2_4_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/xen.12066"},{"key":"e_1_2_4_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms11138"},{"key":"e_1_2_4_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.athoracsur.2019.08.090"},{"key":"e_1_2_4_9_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.667093"},{"key":"e_1_2_4_10_1","doi-asserted-by":"publisher","DOI":"10.1111\/xen.12744"},{"issue":"2","key":"e_1_2_4_11_1","doi-asserted-by":"crossref","first-page":"e12664","DOI":"10.1111\/xen.12664","article-title":"Growth 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