Vascularized Bone Marrow Plays a Critical Role in Inducing Tolerance of Osteomyocutaneous Allografts

C.-H. Lin,¹ M. Anggelia,¹ Y.-L. Wang,¹ H.-Y. Cheng,¹ W. Lee,² G. Brandacher.²

¹Center for Vascularized Composite Allotransplantation, Chang Gung Memorial Hospital, Taipei, Taiwan
²Department of Plastic and Reconstructive Surgery, Johns Hopkins University School of Medicine, Baltimore, MD.

Meeting: 2015 American Transplant Congress

Abstract number: 345

Keywords: Bone marrow transplantation, Co-stimulation, Mixed chimerism, Tolerance

Session Information

Session Name: Concurrent Session: Composite Tissue Allografts: Basic and Translational

Session Type: Concurrent Session

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 May 17, 2025.

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