The success rates of transplant surgery have improved remarkably over the last half century, making this procedure a life-saving option for many patients with organ failure. Early outcomes in transplant recipients are outstanding and patients normally recover from surgery with a well-functioning replacement organ and typically return to an active lifestyle in a short period.

Unfortunately, transplant practice is complicated by the fact that the adult human immune system is strongly biased towards damaging reactions against allogeneic tissues, resulting in total donor organ destruction within a matter of weeks after transplantation, unless the immune system is profoundly inhibited. To impede the immunological response, researchers have developed an armamentarium of general immunosuppressive drugs necessary for sparing transplanted organs from early destruction. During the therapy with immunosuppressive drugs the whole immune system is impaired and a myriad of side-effects arise. Thus, patients maintained on conventional immunosuppressive treatment suffer the consequences of drug toxicity, the development of chronic rejection, reduced resistance to infections, and a high rate of cancer occurrence. Besides these important side effects, financial costs can be high for the families and for health care systems. Added to the reality of presently available treatment options is the fact that 10-year organ survival rates in renal transplantation have astonishingly not shown improvement over the last decades. Improvements in treatment for these patients is imperative.

The ONE Study Focus

Preventing immunological rejection of transplanted organs without the need for long-term use of pharmacological immunosuppression is a primary objective. New transplant research should concentrate on early strategies that support long-term immunological acceptance of transplants, allowing for at least a reduction in the use of general immunosuppression. It would dramatically improve the outcome for transplant recipients and reduce healthcare costs. A means to achieve this goal has not been realized with pharmacological or biological agents, so we must now look towards new, innovative approaches.

The ONE Study applies the novel concept of cell therapy to human clinical organ transplantation. This cooperative project aims at developing and trialling various immunoregulatory cell products in organ transplantation recipients, allowing a direct comparison of the safety, clinical practicality and therapeutic efficacy of each cell type.

The central focus of the ONE Study project is to:

• Produce and manufacture distinct population of ha ematopoietic immunoregulatory cells
• Comparatively study the tolerogenic characteristics of these regulatory cell types
• Test these cell therapy products side by side in a clinical trial living donor renal transplant recipients

The health economics of cell therapy as a new medical technology is another essential aspect of the ONE Study work program that will be fully evaluated. True viability of the proposed new cellular treatments will depend not only on their clinical benefit, but also on an acceptable health-economics profile.