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Chimerism, Transplant Tolerance, and Beyond

Messner, Franka MD1,2; Etra, Joanna W. MD1; Dodd-o, Jeffrey M. MD, PhD3; Brandacher, Gerald MD, FAST1

doi: 10.1097/TP.0000000000002711
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The present review discusses current developments in tolerance induction for solid organ transplantation with a particular emphasis on chimerism-based approaches. It explains the basic mechanisms of chimerism-based tolerance and provides an update on ongoing clinical tolerance trials. The concept of “delayed tolerance” is presented, and ongoing preclinical studies in the nonhuman primate setting—including current limitations and hurdles regarding this approach—are illustrated. In addition, a brief overview and update on cell-based tolerogenic clinical trials is provided. In a critical approach, advantages, limitations, and potential implications for the future of these different regimens are discussed.

1 Department of Plastic and Reconstructive Surgery, Vascularized Composite Allotransplantation (VCA) Laboratory, Johns Hopkins University School of Medicine, Baltimore, MD.

2 Department of Visceral, Transplant and Thoracic Surgery, Center of Operative Medicine, Medical University of Innsbruck, Innsbruck, Austria.

3 Department of Anesthesiology, Johns Hopkins University School of Medicine, Baltimore, MD.

Received 15 September 2018. Revision received 13 February 2019.

Accepted 27 February 2019.

The authors declare no conflicts of interest.

F.M. performed literature research, conceptualized, wrote, revised the article, and provided figures and tables. G.B. conceptualized, wrote, and revised the article. J.M.D. conceptualized, performed literature research, wrote, and revised the article. J.W.E. assisted in writing and revision of the article. J.M.D. and G.B. are the cosenior authors.

Correspondence: Gerald Brandacher, MD, FAST, Reconstructive Transplantation Program, Department of Plastic and Reconstructive Surgery, Johns Hopkins University School of Medicine, Ross Research Building/Suite 749D, 720 Rutland Avenue, Baltimore, MD 21205. (brandacher@jhmi.edu).

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