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CHARACTERIZING THE IMMUNOMODULATORY PROPERTIES OF CADAVERIC DONOR VERTEBRAL BONE MARROW USED IN HAND TRANSPLANTATION
Presenter: Gerald Brandacher, MD
Co-Authors: Sarkar K; Lemas MV; Bitzan J; Sproul JD; Lee WP; Brandacher G; Cooney DS; Yuan N
Johns Hopkins University School of Medicine

Purpose: In clinical trials of hand transplantation, peri-operative infusion of cadaveric donor vertebral body bone marrow (VBBM) has shown promising immunomodulatory effects (allograft maintenance on low-dose tacrolimus monotherapy). The mechanisms behind VBBM's effects are not well-characterized.

Methods: As in our clinical trials, VBBM was prepared from cadaveric donor vertebral bodies, cryopreserved, then thawed. VBBM samples were stained with monoclonal anti-human antibodies to detect a wide variety of cell populations including subsets of T lymphocyte and mesenchymal stem cell (MSC) populations. Antibodies included those for human CD3, CD4, CD8, CD45RA, CD34, CD25, Foxp3, TCRŒ±Œ? and markers for Th1, Th2, and Th17 cells. MSCs were detected using a commercially available kit to identify CD34-/11b-/19-/45-/HLA-DR- and CD73+CD105+CD90+ or CD271+cells. For comparison, similar analysis was done for conventional iliac-crest bone marrow aspirates from healthy donors. For functional analysis of immunosuppressive properties, mixed lymphocyte reaction assays were performed by co-culturing allogeneically stimulated CFSE-stained lymphocytes with whole bone marrow or flow cytometrically sorted bone marrow subpopulations as regulators.

Results: Detailed characterization of VBBM composition reveals that VBBM contains cell populations with known immunomodulatory properties. Composition is grossly comparable to conventionally obtained bone marrow but may contain higher proportions of mesenchymal stem cells. Functional assay reveals potent immunosuppressive effects from whole bone marrow and from sorted sub-populations. The T regulatory cell population is particularly potent in its immunosuppressive abilities.

Conclusion: VBBM contains cell populations with potent immunomodulatory effects. Upcoming studies include cytokine analysis and donor-specific vs. third-party experiments. Our ongoing immunophenotypical and functional characterization of VBBM helps identify the mechanism behind VBBM's immunomodulatory properties, paving the way towards opportunities to refine the cell product and maximize its effectiveness.


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