Embryonic stem cells and potency to induce transplantation tolerance

In the past 40 years, many protocols have been extensively studied for the induction of sustainable transplantation tolerance which might lead to protection of allografts from immunological injury in the clinical setting. Despite the enormous success in rodents, there is still no established protocol available yet for widespread clinical trials. Whilst clonal deletion, clonal anergy and suppression, now coined regulation, have been elucidated as the key immunological elements of tolerance, a better understanding of these mechanisms has so far done little to improve on the survival of organ transplants in humans. Haematopoietic chimaerism, as previously described by Medawar and colleagues [1], remains the most robust tool for tolerance induction. Unfortunately, bone marrow or haematopoietic stem cell transplantation for patients awaiting solid organ transplantation remains a high risk therapy, due to the dangers of graft-versus-host disease. Most recent data, however, indicate the potential of embryonic stem cells (ESC) to offer a possible solution for low risk induction of multilineage mixed chimaerism and tolerance not involving any immunosuppression, due to their unique property of low immunogenicity and high plasticity. Here, what we know about ESC in various species, and the potency and drawbacks of ESC for widespread clinical use, will be discussed.