Regulatory T Cell-Enriching Microparticles for Promoting Vascularized Composite Allotransplant Survival
Abstract
The purpose of this work is to investigate the ability of engineered biomimetic drug delivery systems to prevent rejection and promote immunological tolerance in the context of composite tissue allotransplantation (CTA). A microparticle-based system engineered to release the Treg-recruiting chemokine CCL22 and particles containing IL-2, TGFb , and rapamycin were fabricated and this triple cocktail was tested for their ability to prevent hindlimb rejection. Recruitment-MP prolonged hindlimb allograft survival indefinitely (>200 days) and promoted donor-specific tolerance. Recruitment-MP treatment enriched Treg populations in allograft skin and draining lymph nodes, and enhanced Treg function without affecting the proliferative capacity of conventional T cells. TRI-MP prolongs rat hindlimb allograft survival indefinitely without long-term systemic immunosuppression. We further demonstrate that this form of local immune therapy imparts systemic, antigen-specific tolerance to hindlimb allograft recipients. Ultimately, this approach has the potential to significantly impact the field of VCA and reconstructive transplantation by minimizing the need for the sustained, multi-drug systemic immunosuppression with its associated long-term toxicity.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 2019
- Accession Number
- AD1090640
Entities
People
- James D Fisher
- Steven R. Little
- Vijay S Gorantla
Organizations
- University of Pittsburgh