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Vascularized Bone Marrow Mechanisms of Immunomodulation.

A. Khalifeh, E. Buckingham, M. Uluer, W. Hassanein, W. Twaddell, C. Drachenberg, A. Nam, S. Bartlett, R. Barth.

University of Maryland School of Medicine, Baltimore, MD

Meeting: 2017 American Transplant Congress

Abstract number: B44

Keywords: Bone marrow, Graft survival, T cells

Session Information

Session Name: Poster Session B: Allorecognition and T Cell Biology

Session Type: Poster Session

Date: Sunday, April 30, 2017

Session Time: 6:00pm-7:00pm

 Presentation Time: 6:00pm-7:00pm

Location: Hall D1

Introduction:

Hand and face transplants containing co-transplanted bone may have improved outcomes. We have previously utilized a NHP model to demonstrate that VCA containing VBM have improved outcomes. We designed experiments to explore outcomes of VCA survival after VBM based immunomodulation.

Methods:

Two groups underwent facial VCA with VBM allotransplantation to MHC-mismatched cynomolgus macaques after donor irradiation(Group1; n=4) and donor infusion with antithymocyte (Group2; n=3). Immunospuression consisted of FK and MMF until POD100. End points were graft rejection, flow cytometry with donor-specificc antibodies assessed chimerism.

Results:

Recipients from both groups had early graft loss (Grp1: 32±21 days, Grp2: 35±26 days) secondary to severe rejection. Chimerism in peripheral blood was undetectable in 3/4 animals of grp1 and 2/3 of grp2. Graft bone marrow showed replacement with recipient cells. Deep tissue except bone, showed moderate to severe rejection in animals of both groups. This was compared to our historical VCA with VBM that had mean survival of 348±86 day , 75% chimerism and viable donor VBM.

Conclusion:

These data support that VBM based immunomodulation appears to be based on a locally active cell population that is both radiosensitive and susceptible to T cell depletion. This supports an evolving hypothesis that a cotransplanted cell population within the VBM component of VCA contributes to local regulation of immune responses first activated against donor skin.

CITATION INFORMATION: Khalifeh A, Buckingham E, Uluer M, Hassanein W, Twaddell W, Drachenberg C, Nam A, Bartlett S, Barth R. Vascularized Bone Marrow Mechanisms of Immunomodulation. Am J Transplant. 2017;17 (suppl 3).

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To cite this abstract in AMA style:

Khalifeh A, Buckingham E, Uluer M, Hassanein W, Twaddell W, Drachenberg C, Nam A, Bartlett S, Barth R. Vascularized Bone Marrow Mechanisms of Immunomodulation. [abstract]. Am J Transplant. 2017; 17 (suppl 3). https://atcmeetingabstracts.com/abstract/vascularized-bone-marrow-mechanisms-of-immunomodulation/. Accessed May 8, 2025.

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