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dc.contributor.authorShockcor, Nicole
dc.contributor.authorBuckingham, Evan B
dc.contributor.authorHassanein, Wessam
dc.contributor.authorDhru, Urmil
dc.contributor.authorKhalifeh, Ali
dc.contributor.authorUluer, Mehmet
dc.contributor.authorWoodall, Jhade
dc.contributor.authorBrazio, Philip
dc.contributor.authorDrachenberg, Cynthia
dc.contributor.authorNam, Arthur J
dc.contributor.authorBarth, Rolf N
dc.date.accessioned2021-04-28T15:17:56Z
dc.date.available2021-04-28T15:17:56Z
dc.date.issued2021-01-26
dc.identifier.urihttp://hdl.handle.net/10713/15534
dc.description.abstractBackground: Vascularized composite allografts (VCA) have demonstrated good clinical outcomes dependent on chronic immunosuppression. Previous work by our group and others supports that cotransplanted vascularized bone marrow (VBM) as a component of VCA offers immunologic protection to prolong graft survival. We aimed to characterize the requirements and potential mechanisms of VBM-mediated protection of VCA by modifying grafts through various strategies. Methods: Experimental groups of mismatched cynomolgus macaque recipients received VCA transplants modified by the following approaches: heterotopic separation of the VCA and VBM components; T-cell depletion of either donor or recipient; irradiation of donor VCA; and infusion of donor bone marrow. All groups received standard immunosuppression with tacrolimus and mycophenolate mofetil. Results: Experimental modifications to donor, recipient, or graft all demonstrated short-graft survivals (31 d). Chimerism levels without bone marrow infusion were transient and minimal when detected and were not associated with prolonged survival. Donor bone marrow infusion increased levels of chimerism but resulted in alloantibody production and did not improve graft survival. Conclusions: VCA graft survival is significantly reduced compared with previously reported VCA with VBM transplants (348 d; P = 0.01) when the hematopoietic niche is removed, altered, or destroyed via irradiation, depletion, or topographical rearrangement. These experimental manipulations resulted in similar outcomes to VCA grafts without cotransplanted VBM (25 d). These data support the presence of a radiosensitive, T-cell population within the VBM compartment not reconstituted by reinfusion of bone marrow cells.en_US
dc.description.urihttps://doi.org/10.1097/TXD.0000000000001107en_US
dc.language.isoenen_US
dc.publisherWolters Kluwer Healthen_US
dc.relation.ispartofTransplantation Directen_US
dc.rightsCopyright © 2021 The Author(s). Transplantation Direct. Published by Wolters Kluwer Health, Inc.en_US
dc.subjectcotransplantationen_US
dc.subjectvascularized bone marrowen_US
dc.subject.meshComposite Tissue Allograftsen_US
dc.titleVascularized Bone Marrow Cellular Depletion or Discontinuity Abrogates Protection of Vascularized Composite Allografts in Nonhuman Primatesen_US
dc.typeArticleen_US
dc.identifier.doi10.1097/TXD.0000000000001107
dc.identifier.pmid33521248
dc.source.volume7
dc.source.issue2
dc.source.beginpagee659
dc.source.endpage
dc.source.countryUnited States


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