Harnessing Apoptotic Cells for Transplantation Tolerance: Current Status and Future Perspectives
Purpose of Review
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.
KeywordsApoptotic cells Transplantation Tolerance Suppressor cells Sensitization Nanoparticles
This work was supported by grants from the National Institutes of Health P01 AI112522 (A.D.), U01 AI102463 (X.L.), and R01 EB009910 (X.L.).
A.D. and X.L. conceptualized and wrote the manuscript. X.L. edited and finalized the manuscript.
Compliance with Ethical Standards
Conflict of Interest
The authors declare that they have no conflict of interest.
Human and Animal Rights and Informed Consent
This article does not contain any studies with human or animal subjects performed by any of the authors.
Papers of particular interest, published recently, are highlighted as: • Of importance •• Of major importance
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