Since the mortality rates five years after many solid organ transplants are similar to the mortality rates five years after the first diagnosis of many common cancers, new therapeutic strategies for transplant recipients are desperately needed. While academia continues to produce the basic knowledge required to discover and develop more effective, safer and more cost-effective therapeutics, industry and academia must work together to conduct the clinical trials required for regulatory approval of improved therapeutics. Despite the current unmet clinical need for improved therapeutics, there is a gap in needed expertise and new approaches between where basic science ends and where later stages of clinical trial development begin. Solutions to bridge this gap will be proposed suggesting that the answer to the question is that academia, industry as well as new organizations that bridge this gap are all needed for the creation of new therapeutics.

A principal aim of research in transplantation is to develop strategies that enhance allograft outcomes with minimal cost (side-effects) to patients. Basic scientists can help achieve this goal by probing the fundamental mechanisms of rejection. In this lecture, vignettes from both innate and adaptive immunity will be presented to illustrate this point and a provocative appeal for a return to fundamental, hypothesis-testing science in transplantation will be put forth.

Traditional views of cell death include programmed apoptosis and uncontrolled necrosis. It appears now that both are programmed and have emerging therapeutics, and that caspase-8 – which is involved in apoptosis – may function primarily to control necrosis. The implications for transplantation are tremendous, as organ injury is invariably caused by the procurement and storage procedure, and intervention without understanding the complex biology will have unintended complications.

Our approach to organ preservation has been based on cold storage in buffer solutions, which can augment ischemia reperfusion injury. It may be time to change our views based on new basic and clinical research data. However, is this acceptable for all organs and can the lessons from liver be generalized? Dr. Friend will discuss the development of his exciting OrganOx system from animal models to first-in-human clinical trials currently being conducted at King’s College Hospital in London.

Interventions aimed at ameliorating early organ injury thereby improving early organ function face unique challenges in translation, including clinical trial design and the extreme challenge of conducting trials in DBD (and DCD) donors as injury begins in the deceased donor. However, the administration of novel agents to deceased donors is fraught with ethical, logistical, and regulatory barriers that obstruct innovation. There is a broad-based effort involving HRSA, AST, ASTS, AOPO, and other major multi-disciplinary stakeholders to identify, discuss, and potentially resolve the key barriers.

Progress in terms of ex vivo preparation of Tregs including obtaining sufficient amplification; purity/activity has finally made this approach feasible. Trials in autoimmune disease (Bluestone), and approaches for trials in transplantation are underway, as well as in GVHD/BMT (Blazar). In non-lymphopenic settings such as transplantation, how can we deal with the effector response and tip the balance towards Tregs if most IS agents inhibit Tregs?

After years of anecdotal reports, mesenchymal stem cells have been used in a sizeable randomized controlled trial and shown to improve early outcomes. In addition to decreasing rejection through anti-inflammatory effects, such cells may aid repair and reduce injury – improving initial function. New studies using these cells to treat subclinical rejection and reduce ischemia reperfusion injury are in progress.

Complement is well-known to be involved in antibody-mediated injury. New studies have implicated complement in the function of both regulatory and effector T cells. The underlying basis of this activity and possible therapeutic applications will be discussed.