Date: Tuesday, May 5, 2015
Session Time: 2:15pm-3:45pm
Presentation Time: 2:51pm-3:03pm
Location: Room 119-A
Background: Vascularized composite allograft (VCA) that includes medullary bone may provide proposed benefits of
vascularized bone marrow transplantation (VBMT), such as a continuous supply of donor bone marrow cells that
facilitate tolerance induction. The influence of VBMT on VCA is not completely understood. We aim to investigate
long-term effects of VBMT by direct comparison of allograft survival when VBMT and conventional bone marrow
transplantation (CBMT) is used in conjunction with a costimulation blockade-based immunosuppression regimen.
Methods: Balb/c mice served as osteomyocutaneous (OMC) or myocutaneous (MC) VCA donors to C57BL/6
recipients. VCA survival was evaluated after (1) MC VCA, n = 6; (2) CBMT (MC VCA+ 3×107 BM cells), n = 7; and (3)
VBMT (OMC), n = 10. Intraperitoneal immunotherapy included costimulation blockade (anti-CD154 1 mg at day 0 and
CTLA4Ig 0.5 mg at day 2) and short-term rapamycin (RPM, 3 mg/kg/day x 7 days, then QOD for 3 weeks). Graft
condition was assessed daily. Donor-specific hematopoietic cell engraftment was measured in recipient blood and
tissues at POD 30, 60, 90 and 120.
Results: VCAs that included vascularized bone marrow (VBMT) demonstrated prolonged graft survival (8 of 10
survived longer than 120 days) compared to the other groups (mean survival was 59 and 61.5 days with MC VCA and
CBMT, respectively). Chimerism in the thymus, spleen, lymph nodes and transplanted bone marrow was identified in
VBMT recipients. Circulating CD4+ and CD8+ T cell levels were suppressed in VBMT and CBMT recipients at POD
30 but suppression was maintained in VBMT recipients only. Data from in vitro mixed lymphocyte reaction and in vivo
skin grafting suggest donor-specific tolerance induction in recipients whose grafts survived beyond 120 days.
Conclusions: VBMT was significantly more effective than CBMT in inducing long-term and donor-specific tolerance in
mice that had undergone combined anti-CD154/CD28-based therapy. Preservation of the vascularized bone marrow
cell microenvironment and secondary cell migration and chimerism formation may be significant factors differentiating
VBMT and CBMT.
To cite this abstract in AMA style:Lin C-H, Anggelia M, Wang Y-L, Cheng H-Y, Lee W, Brandacher G. Vascularized Bone Marrow Plays a Critical Role in Inducing Tolerance of Osteomyocutaneous Allografts [abstract]. Am J Transplant. 2015; 15 (suppl 3). https://atcmeetingabstracts.com/abstract/vascularized-bone-marrow-plays-a-critical-role-in-inducing-tolerance-of-osteomyocutaneous-allografts/. Accessed September 28, 2020.
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