Harnessing Apoptotic Cells for Transplantation Tolerance: Current Status and Future Perspectives

The use of donor apoptotic cells is an emerging therapy for inducing transplantation tolerance. In this review, we will discuss current understanding of mechanisms of this approach, as well as crucial aspects necessary for successful translation of this approach to clinical transplantation.

Transplantation tolerance by donor apoptotic cells is mediated by their homeostatic interaction with recipient phagocytes, and subsequent expansion of suppressor cell populations as well as inhibition of effector T cells via deletion and anergy. To ensure their tolerogenicity, it is critical to procure non-stressed donor cells, and to induce and arrest their apoptosis at the appropriate stage prior to their administration. Equally important is the monitoring of dynamics of recipient immunological status, and its influences on tolerance efficacy and longevity. Emerging concepts and technologies may significantly streamline tolerogen manufacture and delivery of this approach, and smooth its transition to clinical application.

Hijacking homeostatic clearance of donor apoptotic cells is a promising strategy for transplantation tolerance. Timing is now mature for concerted efforts for transitioning this strategy to clinical transplantation.