Accession Number:

AD1095684

Title:

Positioning Vascularized Composite Allotransplantation in the Spectrum of Transplantation

Descriptive Note:

Technical Report,15 Sep 2013,14 Sep 2018

Corporate Author:

Childrens Hospital of Philadelphia Philadelphia United States

Personal Author(s):

Report Date:

2018-12-01

Pagination or Media Count:

26.0

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.

Subject Categories:

  • Medicine and Medical Research

Distribution Statement:

APPROVED FOR PUBLIC RELEASE