Grants We Funded
In 2019, The Plastic Surgery Foundation (The PSF) awarded 33 investigator-initiated projects and allocated $891,274 to support the newest, clinically relevant research in plastic surgery.
The American Society of Plastic Surgeons/PSF leadership is committed to continuing to provide high levels of investigator-initiated research support to ensure that plastic surgeons have the needed research resources to be pioneers and innovators in advancing the practice of medicine.
Search The PSF database to have easy access to full-text grant abstracts from past PSF-funded research projects 2003 to present. All abstracts are the work of the Principal Investigators and were retrieved from their PSF grant applications. Several different filters may be applied to locate abstracts specific to a particular focus area, or PSF funding mechanism.
Tolerance Induction to Composite Tissue Allotransplantation
Xin Xiao Zheng MD
University of Pittsburgh
National Endowment for Plastic Surgery Grant
Hand or Upper Extremity
Nonspecific immunosuppression is the only established method currently available for sustaining a hand transplant that des not differ fundamentally from immunosuppression for organ transplantations. However, the requirement of lifetime immunosuppression to prevent composite tissue allotransplantation (CTA) rejection and the toxicity of immunosuppressive drugs has impeded the widespread clinical application. These complications can be particularly troublesome in CTA recipients who do not suffer from a life-threatening disease. This makes the decision for a risky chronic immunosuppression ethically debatable, and the ideal solution would be to get reliable protocols for inducing CTA tolerance.
Recently emerged importance of regulatory T cells (Treg) in allograft tolerance has lead to the concept that the balance between allospecific T effectors and Treg is crucial to tolerance induction. Enhanced allospecific Treg function has been reported to be necessary to induce allograft tolerance in experimental tolerogenic regimens. Thus, vigorous evaluation of the impact of conventional immunosuppressive drugs on Treg activation, proliferation and function is critical to develop new strategies for CTA tolerance. Cyclosporine (CsA) is a major contributor to improved short-term allograft outcome. However, CsA blocks interleukin-2 (IL-2) transcription and consequent IL-2 dependent regulation, we hypothesize that the addition of IL-2/Fc fusion protein, a long-lasting form of IL-2, to widely used clinic strategy of depletion and CsA will induce immunomodulation and promote hind-limb allograft tolerance. In deed our prelimanary data indicate IL-2/Fc plus anti-lymphcyte serum and CsA permit long-term hind-limb allograft survival.
In this project we will i) further define the mechanisms by which this novel strategy promotes CTA tolerance; ii) develop a clinic relevant immune monitoring system for rejection and tolerance; iii) optimize the treatment protocol to induce CTA tolerance.
Xin Xiao Zheng, MD is an Associate Professor in Surgery, has recently joined the UPMC Division of Plastic and Reconstructive Surgery. He is a Director of Protein Therapeutic Core of Starzl Transplantation Institute of UPMC. Dr. Zheng has made original and significant contributions to the field of the basic mechanisms and therapeutic strategies that generate and maintain peripheral tolerance that involve the roles of co-stimulatory molecules, cytokine milieu, newly identified Tim molecules, activation induced apoptosis, T regulatory cells in autoimmune diseases and allograft rejection and tolerance. By utilizing autoimmune and alloimmune animal models on one hand, and "home-made" fusion proteins as unique experimental and therapeutic reagents, Dr. Zheng has studied the mechanisms of peripheral tolerance and developed novel therapeutic strategies to tip the immune balance towards a cure for autoimmune diseases and allografts tolerance safely. Currently, Dr. Zheng focuses his research on composite tissue transplantation tolerance.