Positioning Vascularized Composite Allotransplantation in the Spectrum of Transplantation
Abstract
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.
Document Details
- Document Type
- Technical Report
- Publication Date
- Dec 01, 2018
- Accession Number
- AD1095684
Entities
People
- Wayne W Hancock