2013-2014

Cold preservation of donor organs is a crucial aspect of organ transplantation, not only to keep the organ viable but also to prevent as much cellular damage as possible during the time the organ is out of the body. Several organ-preservation solutions are available, but they are not satisfactory and as a result organ damage still occurs. Thus, a new cold storage solution that can prevent cellular edema and tissue destruction is needed for the safe preservation of donor organs before they are transplanted into recipients. We have developed a novel cold storage solution that has the potential to minimize cold ischemia-related injuries in donor organs. Preliminary studies have demonstrated our novel polymer-based solution significantly increased cell survival of cultured human endothelial cells at 4oC, and reduced tissue damage of murine hearts during cold storage. However, more preclinical studies are needed to prove our hypothesis and test the efficacy in animal models. In this proposal, we would like to further evaluate the beneficial effect of this polymer-based solution on cold organ preservation using transplantation models.

Progress Report 2014

Solid organ transplantation may be a life-saving treatment in individuals with illnesses that have caused organ failure. However, a challenge remains in preventing graft rejection and eventual graft loss. Organ rejection is caused by the patient’s white blood cells recognizing the donor organ as foreign (hence dangerous) and mounts an immune response to attack the organ. Current strategies to minimize organ rejection include matching recipients with donors according to their genes and by controlling the patient’s immune system with immunosuppressive drugs. Although current immunosuppressive drug therapy has dramatically improved early transplant outcomes, the long-term rate of organ rejection has not decreased substantially and the use of immunosuppressive drugs can induce serious side effects. Therefore, we need a better method of educating the immune system to tolerate a foreign organ. We think that expanding the number of regulatory T cells in transplant patients will help them accept the foreign organ, minimizing the need for life-long immunosuppressive drug therapy. Corticosteroids and Vitamin D are two immunosuppressive drugs that can direct our bodies to make regulatory T cells. Our laboratory has shown that topical application (rubbing onto the skin) of Vitamin D and corticosteroids generates regulatory T cells, and it is less toxic than the traditional oral method of delivering the drugs. We would like to optimize the method of drug delivery through the skin to make regulatory T cells and evaluate its efficacy to prevent organ rejection in laboratory animals. This delivery method is less toxic than administering the same kind of drug orally. In addition, it should prevent long- term side effects in patients: the cream is applied only for a short period before and after transplant, whereas the oral drug must be taken for the rest of a patient’s life.