{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T21:16:05Z","timestamp":1777497365819,"version":"3.51.4"},"reference-count":94,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2015,1,22]],"date-time":"2015-01-22T00:00:00Z","timestamp":1421884800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"name":"NIH","award":["AI 57801"],"award-info":[{"award-number":["AI 57801"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2015,2,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>We sought to define the effects and underlying mechanisms of human, marrow-derived mesenchymal stromal cells (hMSCs) on graft-versus-host disease (GvHD) and graft-versus-leukemia (GvL) activity. Irradiated B6D2F1 mice given C57BL\/6 BM and splenic T cells and treated with hMSCs had reduced systemic GvHD, donor T-cell expansion, and serum TNF\u03b1 and IFN\u03b3 levels. Bioluminescence imaging demonstrated that hMSCs redistributed from lungs to abdominal organs within 72 hours, and target tissues harvested from hMSC-treated allogeneic BMT (alloBMT) mice had less GvHD than untreated controls. Cryoimaging more precisely revealed that hMSCs preferentially distributed to splenic marginal zones and regulated T-cell expansion in the white pulp. Importantly, hMSCs had no effect on in vitro cytotoxic T-cell activity and preserved potent GvL effects in vivo. Mixed leukocyte cultures containing hMSCs exhibited decreased T-cell proliferation, reduced TNF\u03b1, IFN\u03b3, and IL-10 but increased PGE2 levels. Indomethacin and E-prostanoid 2 (EP2) receptor antagonisms both reversed while EP2 agonism restored hMSC-mediated in vitro T-cell suppression, confirming the role for PGE2. Furthermore, cyclo-oxygenase inhibition following alloBMT abrogated the protective effects of hMSCs. Together, our data show that hMSCs preserve GvL activity and attenuate GvHD and reveal that hMSC biodistribute to secondary lymphoid organs wherein they attenuate alloreactive T-cell proliferation likely through PGE2 induction. Stem Cells \u00a02015;33:601\u2013614<\/jats:p>","DOI":"10.1002\/stem.1867","type":"journal-article","created":{"date-parts":[[2014,10,21]],"date-time":"2014-10-21T16:26:11Z","timestamp":1413908771000},"page":"601-614","source":"Crossref","is-referenced-by-count":77,"title":["Human Mesenchymal Stromal Cells Attenuate Graft-Versus-Host Disease and Maintain Graft-Versus-Leukemia Activity Following Experimental Allogeneic Bone Marrow Transplantation"],"prefix":"10.1093","volume":"33","author":[{"given":"Jeffery J.","family":"Auletta","sequence":"first","affiliation":[{"name":"Host Defense Program, Hematology\/Oncology\/BMT and Infectious Diseases Nationwide Children's Hospital, Columbus, Ohio, USA"},{"name":"Department of Pediatrics The Ohio State University, Columbus, Ohio, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Saada K.","family":"Eid","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Case Western Reserve University, Cleveland, Ohio, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Patiwet","family":"Wuttisarnwattana","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering Case Western Reserve University, Cleveland, Ohio, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ines","family":"Silva","sequence":"additional","affiliation":[{"name":"Department of Oncology Sidney Kimmel Cancer Center, Baltimore, Maryland, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Leland","family":"Metheny","sequence":"additional","affiliation":[{"name":"Department of Medicine Case Western Reserve University, Cleveland, Ohio, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Matthew D.","family":"Keller","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Case Western Reserve University, Cleveland, Ohio, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rocio","family":"Guardia-Wolff","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Case Western Reserve University, Cleveland, Ohio, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chen","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Pathology University of Florida School of Medicine, Gainesville, Florida, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fangjing","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Medicine Case Western Reserve University, Cleveland, Ohio, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Theodore","family":"Bowen","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Case Western Reserve University, Cleveland, Ohio, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhenghong","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering Case Western Reserve University, Cleveland, Ohio, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luis A.","family":"Solchaga","sequence":"additional","affiliation":[{"name":"Research & Development, Biomimetic Therapeutics, Franklin, Tennessee, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sudipto","family":"Ganguly","sequence":"additional","affiliation":[{"name":"Department of Oncology Sidney Kimmel Cancer Center, Baltimore, Maryland, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Megan","family":"Tyler","sequence":"additional","affiliation":[{"name":"Department of Oncology Sidney Kimmel Cancer Center, Baltimore, Maryland, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David 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