Exosomes as a Reliable Noninvasive Method for Monitoring VCA Graft Rejection
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 those 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; this is called a vascularized composite allotransplant (VCA). However, even with our current immunosuppressive medicines, the immune system often attacks the new tissue and causes damage. We suggest an innovative idea as to why this occurs: The donor graft announces its arrival by sending out very small nanoparticles, called exosomes, into the blood. These exosomes and the cargo they carry alert the immune system to attack the foreign tissue. This novel hypothesis will be tested in three specific aims: (1) determine the contribution of graft-derived exosomes to VCA rejection; (2) sequence the “cargo” of donor and host-derived exosomes; and (3) modulate exosomes and/or microRNAs to prolong graft survival. Our Reconstructive Transplant Research Program (RTRP) Idea Discovery proposal utilizes a novel experimental model and state-of-the-art techniques to address two important focus areas of the RTRP award mechanism: (1) reduce the risks of VCA-associated immunosuppression by defining the unique mechanisms of VCA immunogenicity and (2) develop reliable non-invasive methods or tools for monitoring VCA graft rejection. Our study will advance this new area of transplantation and improve the overall quality of life for injured military personnel.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Mar 10, 2021
- Source ID
- W81XWH2010367
Entities
People
- Sheri Krams
Organizations
- Stanford University
- United States Army