{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T18:45:17Z","timestamp":1792089917551,"version":"4.4.0"},"reference-count":96,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"1","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation"],"published-print":{"date-parts":[[2025,7,8]]},"abstract":"<jats:p>The increasing demand for donor hearts presents both a critical challenge and a significant opportunity for innovation in cardiac transplantation. Advancements in immunosuppressive regimens and genetic engineering have reignited recent interest in xenotransplantation. Notably, 2 human patients have received genetically modified pig hearts under expanded-access authorization. They survived for 40 and 60 days, with xenograft failure preceding death in both cases. Concurrently, decedent studies have focused on monitoring the short-term physiological function of genetically modified cardiac xenografts in legally brain-dead recipients, representing a novel experimental paradigm for preclinical testing to help bridge the gap between nonhuman primate studies and clinical trials. These contemporary achievements build on a large body of exploratory efforts in cardiac xenotransplantation in nonhuman primates. Despite significant progress in overcoming hyperacute rejection, adaptive cellular and humoral immunological barriers remain. This review aims to critically evaluate the current advancements in xenotransplantation, to explore ongoing challenges, and to discuss the future potential of this innovative approach in addressing the growing demand for donor organs in cardiac transplantation.<\/jats:p>","DOI":"10.1161\/circulationaha.124.070875","type":"journal-article","created":{"date-parts":[[2025,7,7]],"date-time":"2025-07-07T14:00:38Z","timestamp":1751896838000},"page":"58-73","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":15,"title":["Cardiac Xenotransplantation: Current State and Future Directions"],"prefix":"10.1161","volume":"152","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8257-0899","authenticated-orcid":true,"given":"Katherine G.","family":"Phillips","sequence":"first","affiliation":[{"name":"Department of Cardiothoracic Surgery (K.G.P., M.L., N.M.), NYU Langone Health, New York, NY."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1231-1159","authenticated-orcid":true,"given":"Imad","family":"Aljabban","sequence":"additional","affiliation":[{"name":"Transplant Institute (I.A., A.G.), NYU Langone Health, New York, NY."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5803-691X","authenticated-orcid":true,"given":"Daniel H.","family":"Wolbrom","sequence":"additional","affiliation":[{"name":"Columbia Center for Translational Immunology, Columbia University College of Physicians and Surgeons, New York, NY (D.H.W.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4894-2024","authenticated-orcid":true,"given":"Adam","family":"Griesemer","sequence":"additional","affiliation":[{"name":"Transplant Institute (I.A., A.G.), NYU Langone Health, New York, NY."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marzia","family":"Leacche","sequence":"additional","affiliation":[{"name":"Department of Cardiothoracic Surgery (K.G.P., M.L., N.M.), NYU Langone Health, New York, NY."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher","family":"McGregor","sequence":"additional","affiliation":[{"name":"Department of Surgery, University of Minnesota Twin Cities, Minneapolis (C.M.)."},{"name":"Institute of Cardiovascular Sciences, UCL, London, UK (C.M.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5306-070X","authenticated-orcid":true,"given":"Nader","family":"Moazami","sequence":"additional","affiliation":[{"name":"Department of Cardiothoracic Surgery (K.G.P., M.L., N.M.), NYU Langone Health, New York, NY."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIR.0000000000001256"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1001\/jamacardio.2022.2213"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cardfail.2023.07.006"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2212438"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCOUTCOMES.119.005795"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1111\/xen.12744"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-018-0765-z"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.healun.2020.05.004"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1038\/s43856-025-00731-y"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms11138"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2201422"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-024-03429-1"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-023-02471-9"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.1964.03060390034008"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.1985.03360230053022"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1038\/19144"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.120.048186"},{"key":"e_1_3_3_19_2","first-page":"238","article-title":"Effects of cyclosporine and antibody adsorption on pig cardiac xenograft survival in the baboon.","volume":"7","author":"Cooper DK","year":"1988","unstructured":"Cooper DK, Human PA, Lexer G, Rose AG, Rees J, Keraan M, Du Toit E. Effects of cyclosporine and antibody adsorption on pig cardiac xenograft survival in the baboon. J Heart Transplant. 1988;7:238\u2013246.","journal-title":"J Heart Transplant"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/s0966-3274(97)80040-8"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1042\/bj20090835"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1111\/xen.12019"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1111\/xen.12124"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.1031185"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(19)77900-9"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1078942"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm1171"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.1097\/TP.0b013e3182472850"},{"key":"e_1_3_3_29_2","doi-asserted-by":"publisher","DOI":"10.2353\/ajpath.2008.070672"},{"key":"e_1_3_3_30_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1399-3089.2008.00480.x"},{"key":"e_1_3_3_31_2","doi-asserted-by":"publisher","DOI":"10.1111\/xen.12142"},{"key":"e_1_3_3_32_2","doi-asserted-by":"publisher","DOI":"10.1097\/TP.0b013e318203c27d"},{"key":"e_1_3_3_33_2","doi-asserted-by":"publisher","DOI":"10.1111\/xen.12161"},{"key":"e_1_3_3_34_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-020-66311-3"},{"key":"e_1_3_3_35_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1399-3089.2003.00103.x"},{"key":"e_1_3_3_36_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.transproceed.2004.12.057"},{"key":"e_1_3_3_37_2","doi-asserted-by":"publisher","DOI":"10.1097\/00007890-199609270-00005"},{"key":"e_1_3_3_38_2","doi-asserted-by":"publisher","DOI":"10.1111\/xen.12465"},{"key":"e_1_3_3_39_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-6143.2012.04122.x"},{"key":"e_1_3_3_40_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0609661104"},{"key":"e_1_3_3_41_2","doi-asserted-by":"publisher","DOI":"10.1097\/TP.0000000000001267"},{"key":"e_1_3_3_42_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2023.1217809"},{"key":"e_1_3_3_43_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1399-3089.2011.00674.x"},{"key":"e_1_3_3_44_2","doi-asserted-by":"publisher","DOI":"10.1097\/00007890-200208150-00024"},{"key":"e_1_3_3_45_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jtcvs.2005.04.017"},{"key":"e_1_3_3_46_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-6143.2011.03846.x"},{"key":"e_1_3_3_47_2","doi-asserted-by":"publisher","DOI":"10.1111\/ajt.12562"},{"key":"e_1_3_3_48_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1399-3089.2005.00221.x"},{"key":"e_1_3_3_49_2","doi-asserted-by":"publisher","DOI":"10.1016\/s1053-2498(00)00224-2"},{"key":"e_1_3_3_50_2","doi-asserted-by":"publisher","DOI":"10.1155\/2017\/2534653"},{"key":"e_1_3_3_51_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.athoracsur.2019.08.090"},{"key":"e_1_3_3_52_2","doi-asserted-by":"publisher","DOI":"10.1111\/xen.12636"},{"key":"e_1_3_3_53_2","first-page":"205","article-title":"Recovery of cardiac function after pig-to-primate orthotopic heart transplant.","volume":"8","author":"McGregor CG","year":"2008","unstructured":"McGregor CG, Davies W, Oi K. Recovery of cardiac function after pig-to-primate orthotopic heart transplant. Am J Transplant. 2008;8:205\u2013206.","journal-title":"Am J Transplant"},{"key":"e_1_3_3_54_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1399-3089.2010.00620.x"},{"key":"e_1_3_3_55_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jtcvs.2021.07.051"},{"key":"e_1_3_3_56_2","doi-asserted-by":"publisher","DOI":"10.1111\/xen.12637"},{"key":"e_1_3_3_57_2","doi-asserted-by":"publisher","DOI":"10.1111\/xen.12576"},{"key":"e_1_3_3_58_2","doi-asserted-by":"publisher","DOI":"10.1111\/xen.12664"},{"key":"e_1_3_3_59_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.molmet.2018.03.006"},{"key":"e_1_3_3_60_2","doi-asserted-by":"publisher","DOI":"10.1097\/TP.0000000000004765"},{"key":"e_1_3_3_61_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-023-06594-4"},{"key":"e_1_3_3_62_2","doi-asserted-by":"publisher","DOI":"10.1111\/xen.12513"},{"key":"e_1_3_3_63_2","doi-asserted-by":"publisher","DOI":"10.1111\/xen.12303"},{"key":"e_1_3_3_64_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-020-73150-9"},{"key":"e_1_3_3_65_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(23)00775-4"},{"key":"e_1_3_3_66_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-022-25624-1"},{"key":"e_1_3_3_67_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm0397-282"},{"key":"e_1_3_3_68_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.aan4187"},{"key":"e_1_3_3_69_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.aad1191"},{"key":"e_1_3_3_70_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2120238"},{"key":"e_1_3_3_71_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaccas.2022.06.011"},{"key":"e_1_3_3_72_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.xjtc.2024.03.019"},{"key":"e_1_3_3_73_2","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0b013e3181e242a8"},{"key":"e_1_3_3_74_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajt.2024.01.035"},{"key":"e_1_3_3_75_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-024-02972-1"},{"key":"e_1_3_3_76_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.trre.2006.06.005"},{"key":"e_1_3_3_77_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jphs.2018.05.013"},{"key":"e_1_3_3_78_2","doi-asserted-by":"publisher","DOI":"10.1111\/ajt.16930"},{"key":"e_1_3_3_79_2","doi-asserted-by":"publisher","DOI":"10.1001\/jamasurg.2023.2774"},{"key":"e_1_3_3_80_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.healun.2024.07.022"},{"key":"e_1_3_3_81_2","doi-asserted-by":"publisher","DOI":"10.1186\/1741-7015-8-74"},{"key":"e_1_3_3_82_2","doi-asserted-by":"publisher","DOI":"10.1111\/ene.16243"},{"key":"e_1_3_3_83_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.667093"},{"key":"e_1_3_3_84_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2201422"},{"key":"e_1_3_3_85_2","doi-asserted-by":"publisher","DOI":"10.1111\/xen.12776"},{"key":"e_1_3_3_86_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-020-68505-1"},{"key":"e_1_3_3_87_2","doi-asserted-by":"publisher","DOI":"10.1111\/ajt.15916"},{"key":"e_1_3_3_88_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajt.2024.01.016"},{"key":"e_1_3_3_89_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.athoracsur.2018.06.004"},{"key":"e_1_3_3_90_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jtcvs.2013.10.030"},{"key":"e_1_3_3_91_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.117.029375"},{"key":"e_1_3_3_92_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jtcvs.2022.09.001"},{"key":"e_1_3_3_93_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-6143.2009.02877.x"},{"key":"e_1_3_3_94_2","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.129983"},{"key":"e_1_3_3_95_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jtcvs.2021.12.048"},{"key":"e_1_3_3_96_2","doi-asserted-by":"publisher","DOI":"10.21037\/tp-22-664"},{"key":"e_1_3_3_97_2","doi-asserted-by":"publisher","DOI":"10.1111\/xen.12865"}],"container-title":["Circulation"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ahajournals.org\/doi\/full\/10.1161\/CIRCULATIONAHA.124.070875","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,30]],"date-time":"2026-03-30T18:00:23Z","timestamp":1774893623000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ahajournals.org\/doi\/10.1161\/CIRCULATIONAHA.124.070875"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,7,8]]},"references-count":96,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2025,7,8]]}},"alternative-id":["10.1161\/CIRCULATIONAHA.124.070875"],"URL":"https:\/\/doi.org\/10.1161\/circulationaha.124.070875","relation":{},"ISSN":["0009-7322","1524-4539"],"issn-type":[{"value":"0009-7322","type":"print"},{"value":"1524-4539","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,7,8]]},"assertion":[{"value":"2025-07-07","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}