Vascularized composite allografts (VCA) feature an inexhaustible source of donor HSCs, which under proper immunomodulation might be able to migrate into the recipients thymus and differentiate into mature T cells. According to this hypothesis we studied if the bone component of a B6/Balbc/nude VCA is capable of reconstituting a functional immune system (CD3+ T cells in peripheral blood/lymphoid organs) in an immunodeficient B6/SCID recipient.
Material and Methods:
B6 and Balbc (WT/nude) murine vascularized allografts (osteomyocutaneous or myocutaneous grafts) were transplanted heterotopically to B6 (WT/scid) mice using rapamycin for immunosuppression. Flow cytometry of peripheral blood (CD3, CD19) was performed postoperatively. In addition, histopathology (H&E) and immunohistochemistry (CD3, CD4, CD8, CD20) of tissues was performed. To assess immunocompetence, allogeneic skin grafts (B6 and Balb/c) were transplanted to either naÏve B6/nude, naÏve B6/scid or B6/scid mice that prior received a B6/nude or Balbc nude VCA.
The surgical success rate was > 85% in all groups. As expected no CD3+ cells and no rejection of skin allografts were detected in B6/nude and B6/scid controls. B6/scid mice that received B6/nude osteomyocutaneous flaps demonstrated B and T cell immunity. The percentage of CD3+ and CD19+ cells within peripheral blood mononuclear cells steadily increased to 57.7% and 17.1% respectively. Allogeneic skin allografts were rejected 2 weeks after transplantation. However, no B and T cell reconstitution was observed in B6/scid mice receiving B6/nude myocutaneous flaps (without bone component).
The vascularized bone marrow component of VCA provides an effective source of HSCs to restore immunocompetence in T-cell deficient mice. This might explain how the vascularized bone marrow niche of these transplants contributes to chimerism induction and maintenance and facilitates the clinically observed immunoprivilege of VCAs.
To cite this abstract in AMA style:Sucher R, Lin C, Zhang D, Zhang W, Grahammer J, Pratschke J, Lee W, Schneeberger S, Zheng X, Brandacher G. Donor HSCs from the Bone Component of Vascularized Composite Allografts Migrate to Recipient Thymus and Differentiate to Mature T Cells [abstract]. Am J Transplant. 2013; 13 (suppl 5). https://atcmeetingabstracts.com/abstract/donor-hscs-from-the-bone-component-of-vascularized-composite-allografts-migrate-to-recipient-thymus-and-differentiate-to-mature-t-cells/. Accessed April 9, 2020.
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