{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T19:42:18Z","timestamp":1792698138891,"version":"4.5.0"},"reference-count":15,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T00:00:00Z","timestamp":1792627200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T00:00:00Z","timestamp":1792627200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Immunol Res"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>In haploidentical hematopoietic stem cell transplantation (HSCT), the addition of post-transplantation cyclophosphamide (Cy) can help to induce immunotolerance between the donor and haploidentical immune system, preventing graft-versus-host disease between the haploidentical immune system and organs\/ tissues of the recipient. We hypothesized that the situation could be reversed and replicated during the transplantation of allogenic tissue and syngeneic (autologous model) HSCT with post-HSCT Cy. We hypothesized that conditioning (pre-HSCT Cy) causes immunoablation of the recipient, and post-HSCT Cy deletes allo-reactive clones from transplanted HSC thus enabling immunotolerance to simultaneously transplanted tissue (organ). To test this hypothesis, we developed a model of autologous HSCT (syngeneic HSCT) with simultaneous transplantation of allogenic tissue in rat. The study rats received: first immunoablation, then allogenic skin graft and syngeneic HSCT, and later post-transplantation Cy. The administration of Cy before and after syngeneic HSCT with simultaneous transplantation of skin graft prolonged skin graft survival from 3 to 12 days and changed the pattern of rejection. The addition of Cy post-HSCT resulted in a statistically significant increase in TNF\u03b1 secretion before rejection compared to acute rejection without Cy post-HSCT. The sole administration of Cy before and after syngeneic HSCT with simultaneous organ transplantation is not sufficient to achieve full tolerance to allogenic tissue. However, with changes to conditioning or additional immunosuppression, this goal could be achieved.<\/jats:p>","DOI":"10.1007\/s12026-026-09862-3","type":"journal-article","created":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T06:16:27Z","timestamp":1792649787000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Syngeneic hematopoietic stem cell transplantation with post-transplantation cyclophosphamide to induce immune tolerance of allogenic skin graft survival in rat"],"prefix":"10.1007","volume":"74","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0851-0975","authenticated-orcid":false,"given":"Kaja","family":"Kasare\u0142\u0142o","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Renata","family":"Podkowi\u0144ska-Polak","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Piotr","family":"Olejnik","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacek","family":"Dziedziak","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Wrzesie\u0144","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Agnieszka","family":"Cudnoch-J\u0119drzejewska","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emilian","family":"Snarski","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,10,22]]},"reference":[{"key":"9862_CR1","doi-asserted-by":"publisher","unstructured":"Bezinover D, Saner F. Organ transplantation in the modern era Prof. Dmitri Bezinover, Prof. Fuat Saner. BMC Anesthesiol BioMed Cent Ltd. 2019;19(1). https:\/\/doi.org\/10.1186\/s12871-019-0704-z.","DOI":"10.1186\/s12871-019-0704-z"},{"key":"9862_CR2","unstructured":"Editorial Immunosupression in Solid Organ Transplantation: Standard of Care and Future Directions. 2020."},{"issue":"9","key":"9862_CR3","doi-asserted-by":"publisher","first-page":"2121","DOI":"10.1111\/j.1600-6143.2006.01434.x","volume":"6","author":"Y Fudaba","year":"2006","unstructured":"Fudaba Y, Spitzer TR, Shaffer J, et al. Myeloma responses and tolerance following combined kidney and nonmyeloablative marrow transplantation: In vivo and in vitro analyses. Am J Transplant. 2006;6(9):2121\u201333. https:\/\/doi.org\/10.1111\/j.1600-6143.2006.01434.x.","journal-title":"Am J Transplant"},{"issue":"6","key":"9862_CR4","doi-asserted-by":"publisher","first-page":"672","DOI":"10.1097\/TP.0b013e31820a3068","volume":"91","author":"TR Spitzer","year":"2011","unstructured":"Spitzer TR, Sykes M, Tolkoff-Rubin N, et al. Long-term follow-up of recipients of combined human leukocyte antigen-matched bone marrow and kidney transplantation for multiple myeloma with end-stage renal disease. Transplantation. 2011;91(6):672\u20136. https:\/\/doi.org\/10.1097\/TP.0b013e31820a3068.","journal-title":"Transplantation"},{"key":"9862_CR5","doi-asserted-by":"publisher","unstructured":"Scandling JD, Busque S, Dejbakhsh-Jones S, et al. Tolerance and chimerism after renal and hematopoietic-cell transplantation. N Engl J Med. 2008;358(4):362\u20138. https:\/\/doi.org\/10.1056\/NEJMoa074191.","DOI":"10.1056\/NEJMoa074191"},{"issue":"6","key":"9862_CR6","doi-asserted-by":"publisher","first-page":"641","DOI":"10.1016\/j.bbmt.2008.03.005","volume":"14","author":"L Luznik","year":"2008","unstructured":"Luznik L, O\u2019Donnell PV, Symons HJ, et al. HLA-Haploidentical Bone Marrow Transplantation for Hematologic Malignancies Using Nonmyeloablative Conditioning and High-Dose, Posttransplantation Cyclophosphamide. Biol Blood Marrow Transplant. 2008;14(6):641\u201350. https:\/\/doi.org\/10.1016\/j.bbmt.2008.03.005.","journal-title":"Biol Blood Marrow Transplant"},{"issue":"7","key":"9862_CR7","doi-asserted-by":"publisher","first-page":"377","DOI":"10.1053\/bbmt.2002.v8.pm12171484","volume":"8","author":"PV O\u2019Donnell","year":"2002","unstructured":"O\u2019Donnell PV, Luznik L, Jones RJ, et al. Nonmyeloablative bone marrow transplantation from partially HLA-mismatched related donors using posttransplantation cyclophosphamide. Biol Blood Marrow Transplant. 2002;8(7):377\u201386. https:\/\/doi.org\/10.1053\/bbmt.2002.v8.pm12171484.","journal-title":"Biol Blood Marrow Transplant"},{"issue":"6","key":"9862_CR8","first-page":"607e","volume":"30","author":"M Solh","year":"2024","unstructured":"Solh M, Bashey A, Zhang X, et al. Immunosuppression-Free Status at 1 Year after Haploidentical Hematopoietic Cell Transplantation with Post-Transplantation Cyclophosphamide. Transpl Cell Ther. 2024;30(6):607e. 1-607.e8.","journal-title":"Transpl Cell Ther"},{"issue":"2","key":"9862_CR9","doi-asserted-by":"publisher","first-page":"283","DOI":"10.1038\/s41409-019-0684-0","volume":"55","author":"B Sharrack","year":"2020","unstructured":"Sharrack B, Saccardi R, Alexander T, et al. Autologous haematopoietic stem cell transplantation and other cellular therapy in multiple sclerosis and immune-mediated neurological diseases: updated guidelines and recommendations from the EBMT Autoimmune Diseases Working Party (ADWP) and the Joint Accreditation Committee of EBMT and ISCT (JACIE). Bone Marrow Transpl. 2020;55(2):283\u2013306. https:\/\/doi.org\/10.1038\/s41409-019-0684-0.","journal-title":"Bone Marrow Transpl"},{"issue":"2","key":"9862_CR10","doi-asserted-by":"publisher","first-page":"165","DOI":"10.1001\/jama.2018.18743","volume":"321","author":"RK Burt","year":"2019","unstructured":"Burt RK, Balabanov R, Burman J, et al. Effect of Nonmyeloablative Hematopoietic Stem Cell Transplantation vs Continued Disease-Modifying Therapy on Disease Progression in Patients With Relapsing-Remitting Multiple Sclerosis: A Randomized Clinical Trial. JAMA. 2019;321(2):165\u201374. https:\/\/doi.org\/10.1001\/jama.2018.18743.","journal-title":"JAMA"},{"issue":"1","key":"9862_CR11","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1007\/s00005-021-00619-4","volume":"69","author":"K Kasare\u0142\u0142o","year":"2021","unstructured":"Kasare\u0142\u0142o K, Snarski E, Sulejczak D, et al. Post Transplantation Cyclophosphamide Improves Outcome of Autologous Hematopoietic Stem Cell Transplantation in Animal Model of Multiple Sclerosis. Arch Immunol Ther Exp (Warsz). 2021;69(1):1\u20139. https:\/\/doi.org\/10.1007\/s00005-021-00619-4.","journal-title":"Arch Immunol Ther Exp (Warsz)"},{"issue":"1","key":"9862_CR12","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1038\/s41409-018-0318-y","volume":"53","author":"A Chruscinski","year":"2019","unstructured":"Chruscinski A, Atkins H, Clement A, et al. An Open-Label Proof-of-Principle Phase 2A Study to Evaluate Autologous Hematopoietic Stem Cell Transplantation for Allogeneic Organ Transplant Tolerance (ASCOTT). Bone Marrow Transpl. 2019;53(1):19\u2013144. https:\/\/doi.org\/10.1038\/s41409-018-0318-y.","journal-title":"Bone Marrow Transpl"},{"issue":"7","key":"9862_CR13","doi-asserted-by":"publisher","first-page":"1385","DOI":"10.1097\/TP.0000000000002695","volume":"103","author":"JW Etra","year":"2019","unstructured":"Etra JW, Grzelak MJ, Fidder SAJ, et al. A skin rejection grading system for vascularized composite allotransplantation in a preclinical large animal model. Transplantation. 2019;103(7):1385\u201391. https:\/\/doi.org\/10.1097\/TP.0000000000002695.","journal-title":"Transplantation"},{"issue":"8","key":"9862_CR14","doi-asserted-by":"publisher","first-page":"1044","DOI":"10.1001\/ARCHNEUROL.65.8.NOC80042","volume":"65","author":"C Krishnan","year":"2008","unstructured":"Krishnan C, Kaplin AI, Brodsky RA, et al. Reduction of disease activity and disability with high-dose cyclophosphamide in patients with aggressive multiple sclerosis. Arch Neurol. 2008;65(8):1044\u201351. https:\/\/doi.org\/10.1001\/ARCHNEUROL.65.8.NOC80042.","journal-title":"Arch Neurol"},{"issue":"3","key":"9862_CR15","doi-asserted-by":"publisher","first-page":"244","DOI":"10.1016\/S1474-4422(09)70017-1","volume":"8","author":"RK Burt","year":"2009","unstructured":"Burt RK, Loh Y, Cohen B, et al. Autologous non-myeloablative haemopoietic stem cell transplantation in relapsing-remitting multiple sclerosis: a phase I\/II study. Lancet Neurol. 2009;8(3):244\u201353. https:\/\/doi.org\/10.1016\/S1474-4422(09)70017-1.","journal-title":"Lancet Neurol"}],"container-title":["Immunologic Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s12026-026-09862-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s12026-026-09862-3","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s12026-026-09862-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T19:02:04Z","timestamp":1792695724000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s12026-026-09862-3"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,10,22]]},"references-count":15,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,12]]}},"alternative-id":["9862"],"URL":"https:\/\/doi.org\/10.1007\/s12026-026-09862-3","relation":{},"ISSN":["1559-0755"],"issn-type":[{"value":"1559-0755","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,10,22]]},"assertion":[{"value":"24 January 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"18 October 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"22 October 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"Experiments using laboratory animals were performed according to II Warsaw Local Ethics Committee approval (Act no. 57\/2015, with corrections 066\/2016, and WAW2\/188\/2019).","order":1,"name":"Ethics","label":"Ethics approval and consent to participate","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Not applicable.","order":2,"name":"Ethics","label":"Consent for publication","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declare no competing interests.","order":3,"name":"Ethics","label":"Competing interests","group":{"name":"EthicsHeading","label":"Declarations"}}],"article-number":"129"}}