{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,12]],"date-time":"2026-03-12T03:28:31Z","timestamp":1773286111702,"version":"3.50.1"},"reference-count":10,"publisher":"Oxford University Press (OUP)","issue":"8","license":[{"start":{"date-parts":[[2015,6,3]],"date-time":"2015-06-03T00:00:00Z","timestamp":1433289600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2015,8,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title\/>\n                  <jats:p>Mesenchymal stem cells and multipotent adult progenitor cells (MAPCs) have been proposed as novel therapeutics for solid organ transplant recipients with the aim of reducing exposure to pharmacological immunosuppression and its side effects. In the present study, we describe the clinical course of the first patient of the phase I, dose-escalation safety and feasibility study, MiSOT-I (Mesenchymal Stem Cells in Solid Organ Transplantation Phase I). After receiving a living-related liver graft, the patient was given one intraportal injection and one intravenous infusion of third-party MAPC in a low-dose pharmacological immunosuppressive background. Cell administration was found to be technically feasible; importantly, we found no evidence of acute toxicity associated with MAPC infusions.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Significance<\/jats:title>\n                  <jats:p>Liver transplantation is the only definitive treatment for liver failure. However, in order to prevent rejection of the graft, patients must receive lifelong pharmacological immunosuppression, which itself causes clinically significant side effects. This study provides preclinical evidence that mesenchymal stem cells (MSCs) and multipotent adult progenitor cells (MAPCs) can prolong allogeneic solid organ transplant survival in animals by switching the host response toward operational tolerance. To examine the safety and feasibility of MAPC therapy in patients receiving a living-related or dead-before-donation unrelated donor liver graft, the MiSOT-I (Mesenchymal Stem Cells in Solid Organ Transplantation Phase I) trial was designed. The first study patient, a 27-year-old male with liver cirrhosis of unknown etiology, received a living-related adult right liver graft from his brother. MAPC administration in both the operating room (day 0) and intensive care unit (day 2) was feasible, and no evidence was seen of acute complications associated with the cell infusion. The absence of any acute clinical complications of cell infusion is reassuring for the future administration of MAPCs.<\/jats:p>\n               <\/jats:sec>","DOI":"10.5966\/sctm.2015-0002","type":"journal-article","created":{"date-parts":[[2015,6,4]],"date-time":"2015-06-04T03:55:38Z","timestamp":1433390138000},"page":"899-904","source":"Crossref","is-referenced-by-count":57,"title":["First-in-Human Case Study: Multipotent Adult Progenitor Cells for Immunomodulation After Liver Transplantation"],"prefix":"10.1093","volume":"4","author":[{"given":"Yorick","family":"Soeder","sequence":"first","affiliation":[{"name":"Department of Surgery University Hospital Regensburg, Regensburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Martin","family":"Loss","sequence":"additional","affiliation":[{"name":"Department of Surgery University Hospital Regensburg, Regensburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christian L.","family":"Johnson","sequence":"additional","affiliation":[{"name":"Department of Surgery University Hospital Regensburg, Regensburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"James A.","family":"Hutchinson","sequence":"additional","affiliation":[{"name":"Department of Surgery University Hospital Regensburg, Regensburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jan","family":"Haarer","sequence":"additional","affiliation":[{"name":"Department of Surgery University Hospital Regensburg, Regensburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Norbert","family":"Ahrens","sequence":"additional","affiliation":[{"name":"Institute for Clinical Chemistry, Laboratory Medicine, and Transfusion Medicine, University Hospital Regensburg, Regensburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robert","family":"Offner","sequence":"additional","affiliation":[{"name":"Institute for Clinical Chemistry, Laboratory Medicine, and Transfusion Medicine, University Hospital Regensburg, Regensburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robert J.","family":"Deans","sequence":"additional","affiliation":[{"name":"Athersys Inc., Cleveland, Ohio, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gil","family":"Van Bokkelen","sequence":"additional","affiliation":[{"name":"Athersys Inc., Cleveland, Ohio, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Edward K.","family":"Geissler","sequence":"additional","affiliation":[{"name":"Department of Surgery University Hospital Regensburg, Regensburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hans J.","family":"Schlitt","sequence":"additional","affiliation":[{"name":"Department of Surgery University Hospital Regensburg, Regensburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marc H.","family":"Dahlke","sequence":"additional","affiliation":[{"name":"Department of Surgery University Hospital Regensburg, Regensburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2015,6,3]]},"reference":[{"key":"2021122704332169000_R1","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1080\/14653240600855905","article-title":"Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement","volume":"8","author":"Dominici","year":"2006","journal-title":"Cytotherapy"},{"key":"2021122704332169000_R2","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1111\/j.1749-6632.2001.tb03593.x","article-title":"Characterization of multipotent adult progenitor cells, a subpopulation of mesenchymal stem cells","volume":"938","author":"Reyes","year":"2001","journal-title":"Ann N Y Acad Sci"},{"key":"2021122704332169000_R3","doi-asserted-by":"crossref","first-page":"595","DOI":"10.5966\/sctm.2012-0166","article-title":"Heart grafts tolerized through third-party multipotent adult progenitor cells can be retransplanted to secondary hosts with no immunosuppression","volume":"2","author":"Eggenhofer","year":"2013","journal-title":"Stem Cells Translational Medicine"},{"key":"2021122704332169000_R4","doi-asserted-by":"crossref","first-page":"3933","DOI":"10.4049\/jimmunol.181.6.3933","article-title":"Pretransplant infusion of mesenchymal stem cells prolongs the survival of a semiallogeneic heart transplant through the generation of regulatory T cells","volume":"181","author":"Casiraghi","year":"2008","journal-title":"J Immunol"},{"key":"2021122704332169000_R5","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1016\/j.trim.2008.08.004","article-title":"Mesenchymal stem cells can induce long-term acceptance of solid organ allografts in synergy with low-dose mycophenolate","volume":"20","author":"Popp","year":"2008","journal-title":"Transpl Immunol"},{"key":"2021122704332169000_R6","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1186\/1745-6215-13-211","article-title":"Treatment-emergent adverse events after infusion of adherent stem cells: The MiSOT-I score for solid organ transplantation","volume":"13","author":"Dillmann","year":"2012","journal-title":"Trials"},{"key":"2021122704332169000_R7","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1186\/1479-5876-9-124","article-title":"Safety and feasibility of third-party multipotent adult progenitor cells for immunomodulation therapy after liver transplantation\u2014A phase I study (MISOT-I)","volume":"9","author":"Popp","year":"2011","journal-title":"J Transl Med"},{"key":"2021122704332169000_R8","doi-asserted-by":"crossref","first-page":"730","DOI":"10.1080\/14653240802320245","article-title":"Pre-clinical safety testing supporting clinical use of allogeneic multipotent adult progenitor cells","volume":"10","author":"Kovacsovics-Bankowski","year":"2008","journal-title":"Cytotherapy"},{"key":"2021122704332169000_R9","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1186\/2047-1440-2-17","article-title":"Standardization of whole blood immune phenotype monitoring for clinical trials: Panels and methods from the ONE study","volume":"2","author":"Streitz","year":"2013","journal-title":"Transp Res"},{"key":"2021122704332169000_R10","first-page":"17","article-title":"Global characterization and genomic stability of human multistem, a multipotent adult progenitor cell","volume":"4","author":"Boozer","year":"2009","journal-title":"J Stem Cells"}],"container-title":["Stem Cells Translational Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.5966%2Fsctm.2015-0002","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.5966%2Fsctm.2015-0002","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/academic.oup.com\/stcltm\/article-pdf\/4\/8\/899\/41864321\/stcltm_4_8_899.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/stcltm\/article-pdf\/4\/8\/899\/41864321\/stcltm_4_8_899.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,1,19]],"date-time":"2022-01-19T02:49:24Z","timestamp":1642560564000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/stcltm\/article\/4\/8\/899-904\/6397306"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,6,3]]},"references-count":10,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2015,6,3]]},"published-print":{"date-parts":[[2015,8,1]]}},"URL":"https:\/\/doi.org\/10.5966\/sctm.2015-0002","relation":{},"ISSN":["2157-6564","2157-6580"],"issn-type":[{"value":"2157-6564","type":"print"},{"value":"2157-6580","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2015,8,1]]},"published":{"date-parts":[[2015,6,3]]}}}