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Cryopreservation and Transplantation of Vascularized Composite Transplants: Unique Challenges and Opportunities

Shani, Nir Ph.D.; Friedman, Or M.D.; Arav, Amir D.V.M., Ph.D.; Natan, Yehudit M.Sc.; Gur, Eyal M.D.

Plastic and Reconstructive Surgery: May 2019 - Volume 143 - Issue 5 - p 1074e-1080e
doi: 10.1097/PRS.0000000000005541
Reconstructive: Trunk: Original Articles

Summary: Vascularized composite allotransplantation is the ultimate reconstructive tool when no other means of reconstruction are available. Despite its immense potential, the applicability of vascularized composite allotransplantation is hampered by high rejection rates and the requirement for high doses of immunosuppressive drugs that are associated with severe adverse effects and death. Because this is a non–life-saving procedure, widespread use of vascularized composite allotransplantation demands methods that will allow the reduction or elimination of immunosuppressive therapy. Efficient methods for the cryopreservation of biological cells and tissues have been sought for decades. The primary challenge in the preservation of viable tissue in a frozen state is the formation of intracellular and extracellular ice crystals during both freezing and thawing, which cause irreversible damage to the tissue. Recent proof-of-concept transplantations of a complete cryopreserved and thawed hindlimb in a rat model have demonstrated the potential of such methods. In the current review, the authors discuss how limb cryopreservation can attenuate or eliminate allograft rejection by either enabling better human leukocyte antigen matching or by adaptation of clinical tolerance protocols such as mixed chimerism induction. Also, the authors discuss the possible advantages of cryopreservation in autologous tissue salvage and cryopreservation following trauma. Clinical-grade cryopreservation may revolutionize the field of reconstruction, organ banking, and complex traumatic limb injury management.

Tel Aviv and Nes-Ziona, Israel

From the Department of Plastic and Reconstructive Surgery, Tel Aviv Sourasky Medical Center, Sackler Faculty of Medicine, Tel Aviv University; and A. A. Cash Technology Ltd.

Received for publication April 19, 2018; accepted October 4, 2018.

Disclosure:Prof. Amir Arav is an inventor on various patents involving the directional freezing technology. The remaining authors have no financial interests to declare.

Eyal Gur, M.D., Department of Plastic and Reconstructive Surgery, Tel Aviv Sourasky Medical Center, Sackler Faculty of Medicine, Tel Aviv University, Weizmann 6, Tel Aviv, Israel,

Copyright © 2019 by the American Society of Plastic Surgeons