{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,6]],"date-time":"2026-02-06T22:37:20Z","timestamp":1770417440687,"version":"3.49.0"},"reference-count":74,"publisher":"Oxford University Press (OUP)","issue":"11","license":[{"start":{"date-parts":[[2022,1,25]],"date-time":"2022-01-25T00:00:00Z","timestamp":1643068800000},"content-version":"vor","delay-in-days":181,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2021,7,28]],"date-time":"2021-07-28T00:00:00Z","timestamp":1627430400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2021,7,28]],"date-time":"2021-07-28T00:00:00Z","timestamp":1627430400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"name":"Meredith Cowden Foundation"},{"DOI":"10.13039\/100005171","name":"Ohio Board of Regents","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100005171","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100008136","name":"Case Western Reserve University","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100008136","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Stadler Family Charitable Foundation"},{"DOI":"10.13039\/100005171","name":"Ohio Board of Regents","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100005171","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100008136","name":"Case Western Reserve University","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100008136","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2021,11,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Graft-vs-host disease (GvHD) limits successful outcomes following allogeneic blood and marrow transplantation (allo-BMT). We examined whether the administration of human, bone marrow-derived, multipotent adult progenitor cells (MAPCs\u2122) could regulate experimental GvHD. The immunoregulatory capacity of MAPC cells was evaluated in vivo using established murine GvHD models. Injection of MAPC cells on day +1 (D1) and +4 (D4) significantly reduced T-cell expansion and the numbers of donor-derived, Tumor Necrosis Factor Alpha (TNF\u03b1) and Interferon Gamma (IFN\u03b3)-producing, CD4+ and CD8+ cells by D10 compared with untreated controls. These findings were associated with reductions in serum levels of TNF\u03b1 and IFN\u03b3, intestinal and hepatic inflammation and systemic GvHD as measured by survival and clinical score. Biodistribution studies showed that MAPC cells tracked from the lung and to the liver, spleen, and mesenteric nodes within 24\u2009hours after injection. MAPC cells inhibited mouse T-cell proliferation in vitro and this effect was associated with reduced T-cell activation and inflammatory cytokine secretion and robust increases in the concentrations of Prostaglandin E2 (PGE2) and Transforming Growth Factor Beta (TGF\u03b2). Indomethacin and E-prostanoid 2 (EP2) receptor antagonism both reversed while EP2 agonism restored MAPC cell-mediated in vitro T-cell suppression, confirming the role for PGE2. Furthermore, cyclo-oxygenase inhibition following allo-BMT abrogated the protective effects of MAPC cells. Importantly, MAPC cells had no effect on the generation cytotoxic T lymphocyte activity in vitro, and the administration of MAPC cells in the setting of leukemic challenge resulted in superior leukemia-free survival. Collectively, these data provide valuable information regarding the biodistribution and regulatory capacity of MAPC cells, which may inform future clinical trial design.<\/jats:p>","DOI":"10.1002\/stem.3434","type":"journal-article","created":{"date-parts":[[2021,11,11]],"date-time":"2021-11-11T09:59:27Z","timestamp":1636624767000},"page":"1506-1519","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Human Multipotent Adult Progenitor Cells Effectively Reduce Graft-vs-Host Disease While Preserving Graft-Vs-Leukemia Activity"],"prefix":"10.1093","volume":"39","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1980-9999","authenticated-orcid":false,"given":"Leland","family":"Metheny","sequence":"first","affiliation":[{"name":"University Hospitals Seidman Cancer Center, Cleveland, Ohio, USA"},{"name":"Case Comprehensive Cancer Center, Cleveland, Ohio, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Saada","family":"Eid","sequence":"additional","affiliation":[{"name":"Department of Pediatrics \u00a0Case Western Reserve University, Cleveland, Ohio, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Patiwet","family":"Wuttisarnwattana","sequence":"additional","affiliation":[{"name":"Department of Computer Engineering \u00a0Chiang Mai University, Chiang Mai, Thailand"},{"name":"Department of Biomedical Engineering Center \u00a0Chiang Mai University, Chiang Mai, Thailand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jeffery J.","family":"Auletta","sequence":"additional","affiliation":[{"name":"Host Defense Program, Hematology, Oncology, and Infectious Diseases \u00a0Nationwide Children's Hospital, Columbus, Ohio, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chen","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Pathology \u00a0Yale School of Medicine, New Haven, Connecticut, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alana","family":"Van Dervort","sequence":"additional","affiliation":[{"name":"Department of Pediatrics \u00a0Case Western Reserve University, Cleveland, Ohio, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Conner","family":"Paez","sequence":"additional","affiliation":[{"name":"Department of Pediatrics \u00a0Case Western Reserve University, Cleveland, Ohio, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"ZhengHong","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering \u00a0Case Western Reserve University, Cleveland, Ohio, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David","family":"Wilson","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering \u00a0Case Western Reserve University, Cleveland, Ohio, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hillard M.","family":"Lazarus","sequence":"additional","affiliation":[{"name":"University Hospitals Seidman Cancer Center, Cleveland, Ohio, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robert","family":"Deans","sequence":"additional","affiliation":[{"name":"Athersys, Inc, Cleveland, Ohio, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wouter","family":"Vant Hof","sequence":"additional","affiliation":[{"name":"Athersys, Inc, Cleveland, Ohio, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yiouli","family":"Ktena","sequence":"additional","affiliation":[{"name":"Department of Oncology \u00a0Johns Hopkins Sidney Kimmel Comprehensive Cancer Center, Baltimore, Maryland, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kenneth R.","family":"Cooke","sequence":"additional","affiliation":[{"name":"Department of Oncology \u00a0Johns Hopkins 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