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dc.contributor.authorO'Flynn, Lisa
dc.contributor.authorTreacy, Oliver
dc.contributor.authorRyan, Aideen E.
dc.contributor.authorMorcos, Maurice
dc.contributor.authorCregg, Marese
dc.contributor.authorGerlach, Jared
dc.contributor.authorJoshi, Lokesh
dc.contributor.authorNosov, Mikhail
dc.contributor.authorRitter, Thomas
dc.date.accessioned2015-12-04T12:31:44Z
dc.date.available2015-12-04T12:31:44Z
dc.date.issued2013-08
dc.identifier.citationO'Flynn, Lisa, Treacy, Oliver, Ryan, Aideen E., Morcos, Maurice, Cregg, Marese, Gerlach, Jared, . . . Ritter, Thomas. (2013). Donor Bone Marrow–derived Dendritic Cells Prolong Corneal Allograft Survival and Promote an Intragraft Immunoregulatory Milieu. Molecular Therapy, 21(11), 2102-2112. doi: http://dx.doi.org/10.1038/mt.2013.167en_IE
dc.identifier.issn1525-0024
dc.identifier.urihttp://hdl.handle.net/10379/5371
dc.descriptionJournal articleen_IE
dc.description.abstractInvestigations into cell therapies for application in organ transplantation have grown. Here, we describe the ex vivo generation of donor bone marrow-derived dendritic cells (BMDCs) and glucocorticoid-treated BMDCs with potent immunomodulatory properties for application in allogeneic transplantation. BMDCs were treated with dexamethasone (Dexa) to induce an immature, maturation-resistant phenotype. BMDC and Dexa BMDC phenotype, antigen presenting cell function, and immunomodulatory properties were fully characterized. Both populations display significant immunomodulatory properties, including, but not limited to, a significant increase in mRNA expression of programmed death-ligand 1 and indoleamine 2,3-dioxygenase. BMDCs and Dexa BMDCs display a profound impaired capacity to stimulate allogeneic lymphocytes. Moreover, in a fully MHC I/II mismatched rat corneal transplantation model, injection of donor-derived, untreated BMDC or Dexa BMDCs (1â Ã â 10(6) cells, day -7) significantly prolonged corneal allograft survival without the need for additional immunosuppression. Although neovascularization was not reduced and evidence of donor-specific alloantibody response was detected, a significant reduction in allograft cellular infiltration combined with a significant increase in the ratio of intragraft FoxP3-expressing regulatory cells was observed. Our comprehensive analysis demonstrates the novel cellular therapeutic approach and significant effect of donor-derived, untreated BMDCs and Dexa BMDCs in preventing corneal allograft rejection.en_IE
dc.description.sponsorshipScience Foundation Ireland - Grant No. [07/IN.1/B925], 09/SRC-B1794; European Regional Development Funden_IE
dc.formatapplication/pdfen_IE
dc.language.isoenen_IE
dc.publisherNature Publishing Groupen_IE
dc.relation.ispartofMolecular Therapyen
dc.subjectOrgan transplantationen_IE
dc.subjectDonor bone marrow-derived dendritic cells (BMDCs)en_IE
dc.subjectGlucocorticoid-treated BMDCsen_IE
dc.titleDonor bone marrow-derived dendritic cells prolong corneal allograft survival and promote an intragraft immunoregulatory milieu.en_IE
dc.typeArticleen_IE
dc.date.updated2015-11-27T13:12:51Z
dc.identifier.doi10.1038/mt.2013.167
dc.local.publishedsourcehttp://dx.doi.org/10.1038/mt.2013.167en_IE
dc.description.peer-reviewedpeer-reviewed
dc.contributor.funder|~|1267883|~|
dc.internal.rssid7442252
dc.local.contactThomas Ritter, School Of Medicine, Regenerative Medicine Institute, Biosciences, Dangan. 5329 Email: thomas.ritter@nuigalway.ie
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