Harnessing Single-Cell Technologies to Understand and Diagnose Rejection in Clinical Face and Upper Extremity Transplantations
Abstract
Approximately seven million people in the United States every year could benefit from vascularized composite allotransplants (VCAs), such as face and limb transplants, because of traumatic injuries or surgical removal of diseased body parts. Many American Service members are returning from the armed conflicts with devastating injuries and limb loss. Over the last two decades, surgical techniques have advanced to enable the transfer of face or limbs from a deceased donor to patients with severe facial injuries and limb loss. The adoption of this transformative therapy, however, has been limited, mainly because the patient’s immune system identifies the transplanted body parts as foreign, and rejects them. Immune rejection, if not treated promptly, can lead to the loss of the transplants. Acute rejection episodes occur more frequently in face and limb transplants, compared to other transplants of internal organs such as kidney transplants. Researchers do not know exactly why this is the case. Understanding the mechanisms for the difference in rejection rates is important because it may lead us to be able to develop anti-rejection therapies that are specifically targeted for patients with face or limb transplants. In this study, we will take advantage of the recent technological advances in genomic studies to investigate immune rejection in human face and limb transplants in details that have not been possible before. Our team has performed the most face transplants at a single center in the world and has extensive expertise in managing patients who have had face and limb transplants. In this proposed study, we will study the banked samples from these patients collected during rejection and non-rejection time points using a state-of-the-art technique. The results from samples collected during rejection will be compared with samples from patients with benign skin inflammation such as drug eruption. Understanding the rejection process is essential to develop new anti-rejection therapies. Also, if we find that unique molecular changes occur in the transplants during rejection, these may be developed as biomarkers to differentiate rejection from other causes of skin inflammation. Therefore, our study will address the Fiscal Year 2017 Restorative Transplantation Research Focus Areas “Understanding mechanisms of acute immune rejection” and “Graft clinical monitoring.” This study will generate results from samples collected from patients, so the findings can be directly translated to improve the clinical outcomes of future patients. This will allow face and limb transplantation to be more accessible to patients who can benefit from it, including American wounded Warriors. We will use the tissue samples already collected and saved in a biobank so the risks to the patients will be minimal. Because our team has performed one of the largest number of face and upper limb transplants worldwide, translation of our research findings to patient care will be seamless. Our proposed studies are the first of their kind in the field of reconstructive transplant research. Our study will generate data that can be used by the entire field to develop multiple new avenues for future research.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Oct 29, 2018
- Source ID
- W81XWH1810798
Entities
People
- Rachael Clark
Organizations
- United States Army