{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,29]],"date-time":"2026-10-29T17:47:47Z","timestamp":1793296067126,"version":"4.5.0"},"reference-count":41,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"854","funder":[{"DOI":"10.13039\/501100001821","name":"Vienna Science and Technology Fund","doi-asserted-by":"publisher","award":["LS18-031"],"award-info":[{"award-number":["LS18-031"]}],"id":[{"id":"10.13039\/501100001821","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.science.org"],"crossmark-restriction":true},"short-container-title":["Sci. Transl. Med."],"published-print":{"date-parts":[[2026,6,17]]},"abstract":"<jats:p>\n                    Cotransplantation of donor bone marrow (BM) has yielded a therapeutic benefit in clinical trials of kidney transplantation by inducing chimerism-based tolerance, but this was dependent on unfavorable recipient irradiation. Additional regulatory T (T\n                    <jats:sub>reg<\/jats:sub>\n                    ) cell administration can overcome the need for myelosuppression, but this has been demonstrated only in mice so far. Here, we conducted a controlled, phase 1\/2a trial of combined BM and T\n                    <jats:sub>reg<\/jats:sub>\n                    cell therapy in HLA-mismatched living-donor kidney transplantation (NCT03867617). Six patients received polyclonal recipient T\n                    <jats:sub>reg<\/jats:sub>\n                    cells and donor BM cells (BMCs) immediately posttransplant. Immunosuppression consisted of thymoglobulin, belatacept, sirolimus, steroids, and short-course tocilizumab. The control group received no T\n                    <jats:sub>reg<\/jats:sub>\n                    cells, BMCs, or tocilizumab. Total leukocyte donor chimerism was detected across all patients in the study group posttransplantation. This was not observed in any patient belonging to the control group, consequently meeting the primary end point of higher chimerism levels in the study versus control groups (\n                    <jats:italic toggle=\"yes\">P<\/jats:italic>\n                    \u00a0=\u00a00.001). Chimerism was observed across multiple lineages, with up to 4% in T cells. For three patients in the study group, immunosuppression could be minimized to belatacept monotherapy. Antidonor reactivity was decreased in in vitro T cell proliferation assays, suggesting specific downmodulation of the antidonor T cell response. In addition, expansion of antidonor T cell clones was shown by T cell receptor sequencing analysis to be dampened in the study versus control groups. This trial serves as a proof of concept for a combination cell therapy that induces chimerism-based immunomodulation in kidney transplantation without the need for irradiation.\n                  <\/jats:p>","DOI":"10.1126\/scitranslmed.aee6850","type":"journal-article","created":{"date-parts":[[2026,6,17]],"date-time":"2026-06-17T17:58:46Z","timestamp":1781719126000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":1,"title":["Donor bone marrow together with recipient regulatory T cells induces chimerism without irradiation in kidney transplantation"],"prefix":"10.1126","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5159-2796","authenticated-orcid":true,"given":"Thomas","family":"Wekerle","sequence":"first","affiliation":[{"name":"Division of Transplantation, Department of General Surgery, Medical University of Vienna, 1090 Vienna, Austria."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5049-2048","authenticated-orcid":true,"given":"Moritz","family":"Muckenhuber","sequence":"additional","affiliation":[{"name":"Division of Transplantation, Department of General Surgery, Medical University of Vienna, 1090 Vienna, Austria."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8447-1795","authenticated-orcid":true,"given":"Andreas","family":"Heinzel","sequence":"additional","affiliation":[{"name":"Division of Nephrology and Dialysis, Department of Internal Medicine III, Medical University of Vienna, 1090 Vienna, Austria."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna Marianne","family":"Weijler","sequence":"additional","affiliation":[{"name":"Division of Transplantation, Department of General Surgery, Medical University of Vienna, 1090 Vienna, Austria."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2630-0581","authenticated-orcid":true,"given":"Ana F.","family":"David","sequence":"additional","affiliation":[{"name":"Division of Nephrology and Dialysis, Department of Internal Medicine III, Medical University of Vienna, 1090 Vienna, Austria."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6805-0077","authenticated-orcid":true,"given":"Verena","family":"Kainz","sequence":"additional","affiliation":[{"name":"Division of Transplantation, Department of General Surgery, Medical University of Vienna, 1090 Vienna, Austria."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7796-8680","authenticated-orcid":true,"given":"Karin","family":"Hu","sequence":"additional","affiliation":[{"name":"Division of Nephrology and Dialysis, Department of Internal Medicine III, Medical University of Vienna, 1090 Vienna, Austria."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jasmin","family":"Mucha","sequence":"additional","affiliation":[{"name":"Division of Transplantation, Department of General Surgery, Medical University of Vienna, 1090 Vienna, Austria."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8284-401X","authenticated-orcid":true,"given":"Konstantinos","family":"Mengrelis","sequence":"additional","affiliation":[{"name":"Division of Transplantation, Department of General Surgery, Medical University of Vienna, 1090 Vienna, Austria."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4419-6282","authenticated-orcid":true,"given":"Roman","family":"Reindl-Schwaighofer","sequence":"additional","affiliation":[{"name":"Division of Nephrology and Dialysis, Department of Internal Medicine III, Medical University of Vienna, 1090 Vienna, Austria."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Georg A.","family":"B\u00f6hmig","sequence":"additional","affiliation":[{"name":"Division of Nephrology and Dialysis, Department of Internal Medicine III, Medical University of Vienna, 1090 Vienna, Austria."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9358-3820","authenticated-orcid":true,"given":"Bruno","family":"Watschinger","sequence":"additional","affiliation":[{"name":"Division of Nephrology and Dialysis, Department of Internal Medicine III, Medical University of Vienna, 1090 Vienna, Austria."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0863-2876","authenticated-orcid":true,"given":"Georg","family":"Gy\u00f6ri","sequence":"additional","affiliation":[{"name":"Division of Transplantation, Department of General Surgery, Medical University of Vienna, 1090 Vienna, Austria."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Soliman","sequence":"additional","affiliation":[{"name":"Division of Transplantation, Department of General Surgery, Medical University of Vienna, 1090 Vienna, Austria."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7647-215X","authenticated-orcid":true,"given":"Andreas","family":"Salat","sequence":"additional","affiliation":[{"name":"Division of Transplantation, Department of General Surgery, Medical University of Vienna, 1090 Vienna, Austria."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christoph","family":"Schwarz","sequence":"additional","affiliation":[{"name":"Division of Visceral Surgery, Department of General Surgery, Medical University of Vienna, 1090 Vienna, Austria."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-3999-6629","authenticated-orcid":true,"given":"Marlena","family":"Muhm","sequence":"additional","affiliation":[{"name":"Division of Transplantation, Department of General Surgery, Medical University of Vienna, 1090 Vienna, Austria."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Georg","family":"Heinze","sequence":"additional","affiliation":[{"name":"Institute of Clinical Biometrics, Center for Medical Data Science, Informatics, and Intelligent Systems, Medical University of Vienna, 1090 Vienna, Austria."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Wolzt","sequence":"additional","affiliation":[{"name":"Clinical Trials Coordination Centre, Medical University of Vienna, 1090 Vienna, Austria."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3599-8099","authenticated-orcid":true,"given":"Nina","family":"Worel","sequence":"additional","affiliation":[{"name":"Department of Transfusion Medicine and Cell Therapy, Medical University of Vienna, 1090 Vienna, Austria."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michaela","family":"Fortschegger","sequence":"additional","affiliation":[{"name":"St Anna Children\u2019s Cancer Research Institute, 1090 Vienna, Austria."},{"name":"Ludwig Boltzmann Institute for Hematology and Oncology, Medical University of Vienna, 1090 Vienna, Austria."},{"name":"Labdia Labordiagnostik GmbH, 1090 Vienna, Austria."},{"name":"Department of Pediatrics, Medical University of Vienna, 1090 Vienna, Austria."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Lion","sequence":"additional","affiliation":[{"name":"St Anna Children\u2019s Cancer Research Institute, 1090 Vienna, Austria."},{"name":"Ludwig Boltzmann Institute for Hematology and Oncology, Medical University of Vienna, 1090 Vienna, Austria."},{"name":"Labdia Labordiagnostik GmbH, 1090 Vienna, Austria."},{"name":"Department of Pediatrics, Medical University of Vienna, 1090 Vienna, Austria."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2929-6135","authenticated-orcid":true,"given":"Heinz","family":"Regele","sequence":"additional","affiliation":[{"name":"Clinical Institute of Pathology, Medical University of Vienna, 1090 Vienna, Austria."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriela","family":"Berlakovich","sequence":"additional","affiliation":[{"name":"Division of Transplantation, Department of General Surgery, Medical University of Vienna, 1090 Vienna, Austria."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1371-1947","authenticated-orcid":true,"given":"Philip F.","family":"Halloran","sequence":"additional","affiliation":[{"name":"Division of Nephrology and Immunology, University of Alberta, Edmonton, AB T6G 2S2, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2889-2533","authenticated-orcid":true,"given":"Matthias","family":"Edinger","sequence":"additional","affiliation":[{"name":"University Hospital Regensburg, Department of Internal Medicine III, Jos\u00e9 Carreras Centrum for Somatic Cell Therapy, Leibniz Institute of Immunotherapy, 93053 Regensburg, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7544-6275","authenticated-orcid":true,"given":"Rainer","family":"Oberbauer","sequence":"additional","affiliation":[{"name":"Division of Nephrology and Dialysis, Department of Internal Medicine III, Medical University of Vienna, 1090 Vienna, Austria."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"221","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2020081215"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(17)31283-7"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1097\/TP.0000000000003532"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.791725"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa071074"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa074191"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.3003509"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2017.01762"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1038\/74731"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.165.1.1"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.aae0501"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41573-024-01089-x"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.adm8859"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(20)30167-7"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.m3734"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1111\/ajt.16395"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm1688"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1097\/TP.0000000000001559"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-6143.2010.03018.x"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.85911"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.healun.2013.11.004"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2004-01-0086"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2006-06-027409"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajt.2022.09.002"},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbmt.2020.02.016"},{"key":"e_1_3_2_27_2","doi-asserted-by":"publisher","DOI":"10.1111\/ajt.12936"},{"key":"e_1_3_2_28_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-6143.2012.04045.x"},{"key":"e_1_3_2_29_2","doi-asserted-by":"publisher","DOI":"10.1097\/TP.0b013e3181ffbaff"},{"key":"e_1_3_2_30_2","doi-asserted-by":"publisher","DOI":"10.1097\/TP.0000000000005311"},{"key":"e_1_3_2_31_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ebiom.2024.105239"},{"key":"e_1_3_2_32_2","doi-asserted-by":"publisher","DOI":"10.2215\/CJN.13100820"},{"key":"e_1_3_2_33_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-6143.2007.01829.x"},{"key":"e_1_3_2_34_2","doi-asserted-by":"publisher","DOI":"10.1097\/TP.0000000000003617"},{"key":"e_1_3_2_35_2","doi-asserted-by":"publisher","DOI":"10.1097\/TP.0000000000005065"},{"key":"e_1_3_2_36_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajt.2025.01.044"},{"key":"e_1_3_2_37_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.ade6949"},{"key":"e_1_3_2_38_2","doi-asserted-by":"publisher","DOI":"10.3389\/fmed.2020.634260"},{"key":"e_1_3_2_39_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2017.00821"},{"key":"e_1_3_2_40_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(14)71017-4"},{"key":"e_1_3_2_41_2","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.3010760"},{"key":"e_1_3_2_42_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2018.00462"}],"container-title":["Science Translational Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.science.org\/doi\/pdf\/10.1126\/scitranslmed.aee6850","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,17]],"date-time":"2026-06-17T17:58:47Z","timestamp":1781719127000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.science.org\/doi\/10.1126\/scitranslmed.aee6850"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6,17]]},"references-count":41,"journal-issue":{"issue":"854","published-print":{"date-parts":[[2026,6,17]]}},"alternative-id":["10.1126\/scitranslmed.aee6850"],"URL":"https:\/\/doi.org\/10.1126\/scitranslmed.aee6850","relation":{},"ISSN":["1946-6234","1946-6242"],"issn-type":[{"value":"1946-6234","type":"print"},{"value":"1946-6242","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6,17]]},"assertion":[{"value":"2025-12-12","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-04-16","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-06-17","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"eaee6850"}}