Donor bone marrow-derived dendritic cells prolong corneal allograft survival and promote an intragraft immunoregulatory milieu.
O'Flynn, Lisa Treacy, Oliver Ryan, Aideen E. Morcos, Maurice Cregg, Marese Gerlach, Jared Joshi, Lokesh Nosov, Mikhail Ritter, Thomas
O'Flynn, Lisa
Treacy, Oliver
Ryan, Aideen E.
Morcos, Maurice
Cregg, Marese
Gerlach, Jared
Joshi, Lokesh
Nosov, Mikhail
Ritter, Thomas
Loading...
Repository DOI
Publication Date
2013-08
Type
Article
Downloads
Citation
O'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.2013.167
Abstract
Investigations 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.
Funder
|~|1267883|~|
Publisher
Nature Publishing Group
Publisher DOI
10.1038/mt.2013.167
Rights
Attribution-NonCommercial-NoDerivs 3.0 Ireland