Positioning Vascularized Composite Allotransplantation in the Spectrum of Transplantation
Technical Report,15 Sep 2013,14 Sep 2018
Childrens Hospital of Philadelphia Philadelphia United States
Pagination or Media Count:
We have undertaken studies of the immune mechanisms contributing to rejection of vascularized composite allografts VCA in murine models, and how these may be overcome to promote long-term allograft survival. We have now firmly established orthotopic hindlimb and forelimb VCA models in our lab and using these have shown that 3 distinct protocols, namely CD154 monoclonal antibody plus 4 weeks of rapamycin RPM, or CTLA4Ig plus 4 weeks of RPM, or TCR mAb plus RPM, can each achieve long-term VCA survival without maintenance immunosuppression. We have now shown that the efficacy of both protocols is dependent upon a radiation-sensitive donor bone marrow BM cell component, namely CXCR4 Foxp3 donor Treg cells. In addition, some limited prolongation on VCA survival was detected using anti-CXCR3 mAb adoptive transfer of Foxp3 Tregs or using a pan-HDAC inhibitor Trichostatin-A plus RPM. The most important findings of our work are the potential for long-term engraftment using any one of the 3 clinically applicable therapeutic protocols noted above as a result of limited peri-transplant immunotherapy.
- Medicine and Medical Research