Grant: Project Grant

Organ transplantation is lifesaving therapy. However, its potential is diminished by the rejection. Many thousands of patients are waiting for transplantation and the waiting list is growing day by day. Organs are damaged during their and storage using current protocols, which lead to their poor performance post-transplantation and ultimately leads to rejection. Current treatments for organ protection and rejection are suboptimal; life-long immunosuppressants are required for all transplant patients to prevent the rejection. However, immunosuppressants have major side effects including infection, diabetics and cancer. The root cause of the delayed performance and rejection of the transplanted organs is the initial damage of blood vessel lining during organ procurement and preservation which is exacerbated after transplantation. This damage recruit cells and proteins in our immune system upon transplantation, and causes damage to the organs which cannot be self-repaired. Based on our recent discovery, we hypothesize that rebuilding the immunosuppressive blood vessel lining will prevent such injuries and could prevent organ rejection (both immediate and delayed). Thus, in this project, we will develop a novel organ engineering therapy based on an immunosuppressing cell surface modification. This is anticipated to inhibit the immune damage and thus will prevent organ rejection. In this proposal, we will investigate the therapeutic potential of this technology in large animal models of kidney and lung transplantation. If successful, this new immunomodulation approach will help millions of transplant patients and significantly improve their quality of life. Importantly, the new therapy can be applied during the current clinical organ procurement and preservation protocols thus have significant translational potential. The new approach may minimize or eliminate the use of immunosuppressants, thus increasing the health benefits.