{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T06:54:50Z","timestamp":1790060090872,"version":"4.0.1"},"reference-count":39,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"782","content-domain":{"domain":["www.science.org"],"crossmark-restriction":true},"short-container-title":["Sci. Transl. Med."],"published-print":{"date-parts":[[2025,1,22]]},"abstract":"<jats:p>\n            Long-term, immunosuppression-free allograft survival has been induced in human and nonhuman primate (NHP) kidney recipients after nonmyeloablative conditioning and donor bone marrow transplantation (DBMT), resulting in transient mixed hematopoietic chimerism. However, the same strategy has consistently failed in NHP heart transplant recipients. Here, we investigated whether long-term heart allograft survival could be achieved by cotransplanting kidneys from the same donor. Cynomolgus monkeys were transplanted with heart allografts alone or heart and kidney allografts from the same major histocompatibility complex (MHC)\u2013mismatched donors. All animals except one received DBMT, either at the same time or after a 2- to 4-month delay, plus short-term costimulation blockade and calcineurin inhibitor treatment. Long-term, immunosuppression-free heart allograft survival was consistently achieved in heart\/kidney, but not heart-alone, recipients. This was not associated with greater donor\/recipient histocompatibility or altered lymphoid cell reconstitution after conditioning. The maintenance of tolerance after heart\/kidney transplantation was associated with the presence of forkhead box P3 (Foxp3\n            <jats:sup>+<\/jats:sup>\n            ) regulatory T cell (T\n            <jats:sub>reg<\/jats:sub>\n            )\u2013rich organized lymphoid structures in kidneys but not hearts. Substituting high-dose erythropoietin treatment for kidney transplantation was unsuccessful, suggesting that it was not the sole mechanism of action. RNA sequencing analysis revealed that gene expression in hearts from tolerant recipients closely resembled that in hearts from chronically immunosuppressed recipients but differed markedly from rejecting allografts and na\u00efve hearts. A version of this protocol may be able to induce tolerance in patients with end-stage heart and kidney failure who require combined heart and kidney transplantation.\n          <\/jats:p>","DOI":"10.1126\/scitranslmed.ads0255","type":"journal-article","created":{"date-parts":[[2025,1,22]],"date-time":"2025-01-22T18:58:51Z","timestamp":1737572331000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":9,"title":["Cardiac allograft tolerance can be achieved in nonhuman primates by donor bone marrow and kidney cotransplantation"],"prefix":"10.1126","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-5706-6795","authenticated-orcid":true,"given":"Makoto","family":"Tonsho","sequence":"first","affiliation":[{"name":"Center for Transplantation Sciences, Department of Surgery, Massachusetts General Hospital, Boston, MA 02114, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6260-238X","authenticated-orcid":true,"given":"Jane M.","family":"O","sequence":"additional","affiliation":[{"name":"Center for Transplantation Sciences, Department of Surgery, Massachusetts General Hospital, Boston, MA 02114, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3205-3866","authenticated-orcid":true,"given":"Kaitlan","family":"Ahrens","sequence":"additional","affiliation":[{"name":"Center for Transplantation Sciences, Department of Surgery, Massachusetts General Hospital, Boston, MA 02114, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4731-5558","authenticated-orcid":true,"given":"Kortney","family":"Robinson","sequence":"additional","affiliation":[{"name":"Center for Transplantation Sciences, Department of Surgery, Massachusetts General Hospital, Boston, MA 02114, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-1452-1157","authenticated-orcid":true,"given":"Wiebke","family":"Sommer","sequence":"additional","affiliation":[{"name":"Center for Transplantation Sciences, Department of Surgery, Massachusetts General Hospital, Boston, MA 02114, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Svjetlan","family":"Boskovic","sequence":"additional","affiliation":[{"name":"Center for Transplantation Sciences, Department of Surgery, Massachusetts General Hospital, Boston, MA 02114, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3198-1916","authenticated-orcid":true,"given":"Parth M.","family":"Patel","sequence":"additional","affiliation":[{"name":"Center for Transplantation Sciences, Department of Surgery, Massachusetts General Hospital, Boston, MA 02114, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David C.","family":"Becerra","sequence":"additional","affiliation":[{"name":"Center for Transplantation Sciences, Department of Surgery, Massachusetts General Hospital, Boston, MA 02114, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1364-6989","authenticated-orcid":true,"given":"Kyu Ha","family":"Huh","sequence":"additional","affiliation":[{"name":"Center for Transplantation Sciences, Department of Surgery, Massachusetts General Hospital, Boston, MA 02114, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1720-8222","authenticated-orcid":true,"given":"Cynthia L.","family":"Miller","sequence":"additional","affiliation":[{"name":"Center for Transplantation Sciences, Department of Surgery, Massachusetts General Hospital, Boston, MA 02114, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1226-9413","authenticated-orcid":true,"given":"Abbas","family":"Dehnadi","sequence":"additional","affiliation":[{"name":"Center for Transplantation Sciences, Department of Surgery, Massachusetts General Hospital, Boston, MA 02114, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6218-3979","authenticated-orcid":true,"given":"Isabel","family":"Hanekamp","sequence":"additional","affiliation":[{"name":"Center for Transplantation Sciences, Department of Surgery, Massachusetts General Hospital, Boston, MA 02114, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0621-3202","authenticated-orcid":true,"given":"Ivy A.","family":"Rosales","sequence":"additional","affiliation":[{"name":"Department of Pathology, Massachusetts General Hospital, Boston, MA 02114, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4493-4150","authenticated-orcid":true,"given":"Robert B.","family":"Colvin","sequence":"additional","affiliation":[{"name":"Department of Pathology, Massachusetts General Hospital, Boston, MA 02114, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David H.","family":"Sachs","sequence":"additional","affiliation":[{"name":"Center for Transplantation Sciences, Department of Surgery, Massachusetts General Hospital, Boston, MA 02114, USA."},{"name":"Columbia Center for Translational Immunology, Department of Medicine, Columbia University, New York, NY 10032, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0347-1927","authenticated-orcid":true,"given":"Alessandro","family":"Alessandrini","sequence":"additional","affiliation":[{"name":"Center for Transplantation Sciences, Department of Surgery, Massachusetts General Hospital, Boston, MA 02114, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A.","family":"Cosimi","sequence":"additional","affiliation":[{"name":"Center for Transplantation Sciences, Department of Surgery, Massachusetts General Hospital, Boston, MA 02114, USA."},{"name":"Division of Transplantation, Department of Surgery, Massachusetts General Hospital, Boston, MA 02114, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7107-5259","authenticated-orcid":true,"given":"Robert L.","family":"Fairchild","sequence":"additional","affiliation":[{"name":"Department of Inflammation and Immunity, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44195, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paolo","family":"Cravedi","sequence":"additional","affiliation":[{"name":"Translational Transplant Research Center and Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sofia","family":"Bin","sequence":"additional","affiliation":[{"name":"Translational Transplant Research Center and Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA."},{"name":"Nephrology, Dialysis and Kidney Transplant Unit, Scientific Institute for Research, Hospitalization and Healthcare (IRCCS)\u2013Azienda Ospedaliero, University of Bologna, Bologna 40138, Italy."},{"name":"Department of Medical and Surgical Sciences (DIMEC)\u2013Alma Mater Studiorum, University of Bologna, Bologna 40126, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4673-6913","authenticated-orcid":true,"given":"Peter S.","family":"Heeger","sequence":"additional","affiliation":[{"name":"Comprehensive Transplant Center, Cedars-Sinai Medical Center, West Hollywood, CA 90048, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6499-1443","authenticated-orcid":true,"given":"James S.","family":"Allan","sequence":"additional","affiliation":[{"name":"Center for Transplantation Sciences, Department of Surgery, Massachusetts General Hospital, Boston, MA 02114, USA."},{"name":"Division of Thoracic Surgery, Department of Surgery, Massachusetts General Hospital, Boston, MA 02114, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6900-4603","authenticated-orcid":true,"given":"Tatsuo","family":"Kawai","sequence":"additional","affiliation":[{"name":"Center for Transplantation Sciences, Department of Surgery, Massachusetts General Hospital, Boston, MA 02114, USA."},{"name":"Division of Transplantation, Department of Surgery, Massachusetts General Hospital, Boston, MA 02114, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1356-3171","authenticated-orcid":true,"given":"Gilles","family":"Benichou","sequence":"additional","affiliation":[{"name":"Center for Transplantation Sciences, Department of Surgery, Massachusetts General Hospital, Boston, MA 02114, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2724-1333","authenticated-orcid":true,"given":"Joren C.","family":"Madsen","sequence":"additional","affiliation":[{"name":"Center for Transplantation Sciences, Department of Surgery, Massachusetts General Hospital, Boston, MA 02114, USA."},{"name":"Division of Cardiac Surgery, Department of Surgery, Massachusetts General Hospital, Boston, MA 02114, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"221","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.3002093"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1097\/00007890-199912150-00022"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa071074"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1097\/00007890-200206150-00011"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.147.5.1449"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1111\/ajt.12423"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1097\/MOT.0000000000000594"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1038\/223472a0"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.139331"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1097\/00007890-199802150-00002"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-6143.2004.00523.x"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-6143.2006.01703.x"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-6143.2011.03795.x"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1111\/ajt.13130"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1097\/TP.0000000000002078"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1097\/TP.0000000000002470"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajpath.2010.12.024"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2013090945"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1097\/TP.0000000000002867"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1111\/ajt.13131"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1111\/ajt.13489"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-5223(00)70005-5"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-065X.2006.00428.x"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1111\/ajt.13645"},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.1111\/ajt.16880"},{"key":"e_1_3_2_27_2","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.124086"},{"key":"e_1_3_2_28_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.exphem.2007.03.018"},{"key":"e_1_3_2_29_2","doi-asserted-by":"publisher","DOI":"10.1097\/TP.0000000000001559"},{"key":"e_1_3_2_30_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.surg.2004.02.009"},{"key":"e_1_3_2_31_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1523-1755.1998.00800.x"},{"key":"e_1_3_2_32_2","doi-asserted-by":"publisher","DOI":"10.1038\/ni1333"},{"key":"e_1_3_2_33_2","doi-asserted-by":"publisher","DOI":"10.1097\/TP.0000000000002911"},{"key":"e_1_3_2_34_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.athoracsur.2019.02.012"},{"key":"e_1_3_2_35_2","doi-asserted-by":"publisher","DOI":"10.1111\/ajt.15533"},{"key":"e_1_3_2_36_2","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.add5318"},{"key":"e_1_3_2_37_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00251-007-0209-7"},{"key":"e_1_3_2_38_2","doi-asserted-by":"publisher","DOI":"10.1038\/72162"},{"key":"e_1_3_2_39_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.healun.2005.03.019"},{"key":"e_1_3_2_40_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.healun.2013.08.011"}],"container-title":["Science Translational Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.science.org\/doi\/pdf\/10.1126\/scitranslmed.ads0255","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,1,22]],"date-time":"2025-01-22T18:59:12Z","timestamp":1737572352000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.science.org\/doi\/10.1126\/scitranslmed.ads0255"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,1,22]]},"references-count":39,"journal-issue":{"issue":"782","published-print":{"date-parts":[[2025,1,22]]}},"alternative-id":["10.1126\/scitranslmed.ads0255"],"URL":"https:\/\/doi.org\/10.1126\/scitranslmed.ads0255","relation":{},"ISSN":["1946-6234","1946-6242"],"issn-type":[{"value":"1946-6234","type":"print"},{"value":"1946-6242","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,1,22]]},"assertion":[{"value":"2024-07-25","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-12-30","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-01-22","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"eads0255"}}