Generation of Chimeric Thymus for Donor-Specific Tolerance Induction in Vascularized Composite Allotransplantation
Abstract
Rationale and Objectives of Research: Transplantation of hands, faces, and other “body parts” is the newest frontier of organ transplantation. Unlike organs like hearts, livers, or kidneys, these transplants do not “save lives” but rather can “improve quality of life” of patients including our wounded Service members and Veterans that suffer with devastating injuries that have no other treatment options. Also, unlike other organs, composite transplants like hand or face consist of different tissues such as skin, bone, and bone marrow among a host of other components. Since 1998, over 200 of these procedures, including over 100 hands and 30 face transplants have been performed around the world. Although there have been successes, there have been some patient deaths and more importantly there is the lifelong risk of immunosuppressive drugs needed by patients to prevent transplant rejection. Much of the research that has been funded by the military in these transplants has focused on new therapies such as those that use stem cells or bone marrow cells to eliminate the need for such drug treatment. Success has been scant and such therapies have yet to achieve wider feasibility. There is thus a need to investigate alternate, yet promising approaches that are safe, reliable, efficacious, and reproducible in achieving the goal of immunosuppression reduction or elimination after these transplants. The thymus is a central organ of our immune system, which plays a key role in supporting the development of T cells -- the key immune cells in our body that are involved in immunity as well as transplant rejection. It is also the main organ involved in establishing immune “tolerance” through the elimination of those T cells that react against one’s own body. The thymus is the organ that educates the T cells so that they can recognize self and non-self. We envision a strategy of “transplanting” a donor thymus into the recipient thymus to help regulate or tolerize the host immune responses after epigastric flap transplantation. We believe that creating such “chimeric thymus” with donor thymic cells will educate the recipient immune system into believing that the transplanted graft is similar to itself and hence become “tolerant” to it without the necessity for any long-lasting immunosuppression. Our proposal is a major step in breakthrough strategies that modulate or tolerize the graft to the recipient rather than suppressing the recipient immune system towards the graft. If successful, this approach could facilitate long-term rejection-free graft acceptance/survival without lifelong immunosuppression and help benefit our wounded Service members and Veterans suffering from amputations, facial injuries, or genital injuries. This project is a partnership of civilian and military experts across multiple disciplines (transplant immunology, reconstructive surgery, and organ engineering) to bring to fruition a groundbreaking therapy that is safe, ethical, feasible, reproducible, and effective in our wounded Warriors.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Nov 19, 2019
- Source ID
- W81XWH1910011
Entities
People
- Fatih Zor
Organizations
- United States Army
- Wake Forest University