Identification and Therapeutic Targeting of a Novel Cell Population in Rejection of Vascularized Composite Allotransplantation
Abstract
Injuries sustained by military personnel include severe facial injuries and limb amputations that cannot always be adequately reconstructed by plastic surgery, resulting in life-altering disfigurement and disability. Similar to people who receive a life-saving kidney, heart, or liver transplant from a deceased donor, patients with limb loss or catastrophic facial injuries can now receive new tissues, including hands, arms, faces, or legs. However, even with our current immunosuppressive medicines, the immune system often attacks the new tissue and causes damage. If the immune system attacks and damages a kidney, as a last resort, the person can return to dialysis. But what happens to a person when a hand or a face is attacked by the immune system and large doses of immunosuppressive drugs don’t help? This is the difficult challenge we are addressing in the current proposal. Using our newly developed experimental model, we discovered a population of immune cells that “revs” up the immune system and directs immune cells to destroy the transplanted tissue. The goal of the project is to identify these troublemaker immune cells, “turn the tables,” and target them for destruction. We will use a newly developed multiplex, single-cell profiling technology, available in our laboratory, called CyTOF to fully characterize the development of this population of immune cells. Further, we will use tiny nanoparticles to deliver a drug that disarms these troublemaker immune cells and allows the transplanted hand, arm, face, or leg to survive unscathed. Based on our findings, we will develop a non-invasive test that will alert the doctor when the transplant is in danger and more immunosuppressive medicines are necessary. Our Reconstructive Transplant Research Program (RTRP) proposal addresses two important focus areas of the RTRP award mechanism: (1) reduce the risks of VCA-associated immunosuppression and (2) develop reliable non-invasive methods or tools for monitoring VCA graft rejection. Results from our study will improve the quality of life for people who receive hand, arm, leg, or face transplants.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Mar 10, 2021
- Source ID
- W81XWH2010363
Entities
People
- Sheri Krams
Organizations
- Stanford University
- United States Army