Transplantation tolerance in an age of induced pluripotency

In a seminal paper in 2006, Yamanaka and coworkers reported the reprogramming of terminally differentiated murine cells to a pluripotent state, largely indistinguishable from conventional embryonic stem cells. The introduction of defined transcription factors via retroviral transduction revealed, in principle, how pluripotency, once thought to be lost at an early stage of embryogenesis, could be reawakened in adulthood.

Since these initial findings, induced pluripotency has been reported using human as well as mouse cells and through the introduction of recombinant proteins, thereby avoiding the use of retroviruses for genetic modification. This approach, therefore, harnesses the traditional plasticity of embryonic stem cells as a source of therapeutic cell types and tissues, but without the many ethical issues with which they have become synonymous. The potential for exploiting pluripotency in this way also raises the tantalizing prospect of personalized therapies, spawning a new chapter in the story of regenerative medicine.

Given the promise of induced pluripotency and the disarming ease with which it can be achieved, it is perhaps timely to address the likely effect it will have on the field of transplantation and to ask whether the generation of induced pluripotent stem cells of autologous origin is ever likely to render redundant the need for transplantation tolerance.