{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,11]],"date-time":"2025-11-11T22:12:05Z","timestamp":1762899125088,"version":"3.37.3"},"reference-count":31,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2015,4,23]],"date-time":"2015-04-23T00:00:00Z","timestamp":1429747200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"name":"Edward and Dana Slatkin Research Fund"},{"DOI":"10.13039\/100000050","name":"National Heart Lung Blood Institute","doi-asserted-by":"crossref","award":["PO1 HL107146","RO1 HL60528","RO1 HL73714"],"award-info":[{"award-number":["PO1 HL107146","RO1 HL60528","RO1 HL73714"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"crossref"}]},{"name":"American Diabetes Association Basic Science","award":["110151"],"award-info":[{"award-number":["110151"]}]},{"DOI":"10.13039\/100008035","name":"Harvard Stem Cell Institute","doi-asserted-by":"crossref","award":["109210"],"award-info":[{"award-number":["109210"]}],"id":[{"id":"10.13039\/100008035","id-type":"DOI","asserted-by":"crossref"}]},{"name":"postdoctoral fellowship"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2015,5,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Type 1 diabetes (T1D) is an immune-mediated disease resulting in destruction of insulin-producing pancreatic beta cells. Mesenchymal stem cells (MSCs) possess potent immunomodulatory properties, garnering increasing attention as cellular therapy for T1D and other immunologic diseases. However, MSCs generally lack homing molecules, hindering their colonization at inflammatory sites following intravenous (IV) administration. Here, we analyzed whether enforced E-selectin ligand expression on murine MSCs could impact their effect in reversing hyperglycemia in nonobese diabetic (NOD) mice. Although murine MSCs natively do not express the E-selectin-binding determinant sialyl Lewisx (sLex), we found that fucosyltransferase-mediated \u03b1(1,3)-exofucosylation of murine MSCs resulted in sLex display uniquely on cell surface CD44 thereby creating hematopoietic cell E-\/L-selectin ligand (HCELL), the E-selectin-binding glycoform of CD44. Following IV infusion into diabetic NOD mice, allogeneic HCELL+ MSCs showed threefold greater peri-islet infiltrates compared to buffer-treated (i.e., HCELL\u2212) MSCs, with distribution in proximity to E-selectin-expressing microvessels. Exofucosylation had no effect on MSC immunosuppressive capacity in in vitro assays; however, although engraftment was temporary for both HCELL+ and HCELL\u2212 MSCs, administration of HCELL+ MSCs resulted in durable reversal of hyperglycemia, whereas only transient reversal was observed following administration of HCELL\u2212 MSCs. Notably, exofucosylation of MSCs generated from CD44\u2212\/\u2212 mice induced prominent membrane expression of sLex, but IV administration of these MSCs into hyperglycemic NOD mice showed no enhanced pancreatotropism or reversal of hyperglycemia. These findings provide evidence that glycan engineering to enforce HCELL expression boosts trafficking of infused MSCs to pancreatic islets of NOD mice and substantially improves their efficacy in reversing autoimmune diabetes. Stem Cells \u00a02013;33:1523\u20131531<\/jats:p>","DOI":"10.1002\/stem.1948","type":"journal-article","created":{"date-parts":[[2015,1,13]],"date-time":"2015-01-13T01:26:29Z","timestamp":1421112389000},"page":"1523-1531","source":"Crossref","is-referenced-by-count":35,"title":["HCELL Expression on Murine MSC Licenses Pancreatotropism and Confers Durable Reversal of Autoimmune Diabetes in NOD Mice"],"prefix":"10.1093","volume":"33","author":[{"given":"Reza","family":"Abdi","sequence":"first","affiliation":[{"name":"Department of Medicine Renal Division & Transplantation Research Center, Brigham & Women's Hospital, Harvard Medical School Boston, Massachusetts, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robert","family":"Moore","sequence":"additional","affiliation":[{"name":"Department of Medicine Renal Division & Transplantation Research Center, Brigham & Women's Hospital, Harvard Medical School Boston, Massachusetts, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shinobu","family":"Sakai","sequence":"additional","affiliation":[{"name":"Department of Dermatology Harvard Medical School, Boston, Massachusetts, USA"},{"name":"Program of Excellence in Glycosciences Harvard Medical School, Boston, Massachusetts, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Conor B.","family":"Donnelly","sequence":"additional","affiliation":[{"name":"Department of Dermatology Harvard Medical School, Boston, Massachusetts, USA"},{"name":"Program of Excellence in Glycosciences Harvard Medical School, Boston, Massachusetts, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marwan","family":"Mounayar","sequence":"additional","affiliation":[{"name":"Department of Medicine Renal Division & Transplantation Research Center, Brigham & Women's Hospital, Harvard Medical School Boston, Massachusetts, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robert","family":"Sackstein","sequence":"additional","affiliation":[{"name":"Department of Dermatology Harvard Medical School, Boston, Massachusetts, USA"},{"name":"Program of Excellence in Glycosciences Harvard Medical School, Boston, Massachusetts, USA"},{"name":"Department of Medicine Brigham & Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2015,4,23]]},"reference":[{"key":"2022011103312657300_stem1948-bib-0001","doi-asserted-by":"crossref","first-page":"1753","DOI":"10.2337\/dc09-0373","article-title":"Immunotherapy for the prevention and treatment of type 1 diabetes: Optimizing the path from bench to bedside","volume":"32","author":"Bresson","year":"2009","journal-title":"Diabetes Care"},{"key":"2022011103312657300_stem1948-bib-0002","doi-asserted-by":"crossref","first-page":"433","DOI":"10.1056\/NEJMoa1107096","article-title":"GAD65 antigen therapy in recently diagnosed type 1 diabetes mellitus","volume":"366","author":"Ludvigsson","year":"2012","journal-title":"N Engl J Med"},{"key":"2022011103312657300_stem1948-bib-0003","doi-asserted-by":"crossref","first-page":"2214","DOI":"10.2337\/db12-0648","article-title":"Bonifacio E. 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