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Partial freezing of rat livers extends preservation time by 5-fold

Author

Listed:
  • Shannon N. Tessier

    (Harvard Medical School and Massachusetts General Hospital
    Shriners Hospitals for Children Boston)

  • Reinier J. de Vries

    (Harvard Medical School and Massachusetts General Hospital
    Shriners Hospitals for Children Boston
    University of Amsterdam)

  • Casie A. Pendexter

    (Harvard Medical School and Massachusetts General Hospital
    Shriners Hospitals for Children Boston
    Sylvatica Biotech Inc.)

  • Stephanie E. J. Cronin

    (Harvard Medical School and Massachusetts General Hospital
    Shriners Hospitals for Children Boston)

  • Sinan Ozer

    (Harvard Medical School and Massachusetts General Hospital
    Shriners Hospitals for Children Boston)

  • Ehab O. A. Hafiz

    (Theodor Bilharz Research Institute)

  • Siavash Raigani

    (Shriners Hospitals for Children Boston
    Massachusetts General Hospital)

  • Joao Paulo Oliveira-Costa

    (Harvard Medical School and Massachusetts General Hospital
    Harvard Medical School)

  • Benjamin T. Wilks

    (Harvard Medical School and Massachusetts General Hospital
    Shriners Hospitals for Children Boston)

  • Manuela Lopera Higuita

    (Harvard Medical School and Massachusetts General Hospital
    Shriners Hospitals for Children Boston)

  • Thomas M. van Gulik

    (University of Amsterdam)

  • Osman Berk Usta

    (Harvard Medical School and Massachusetts General Hospital
    Shriners Hospitals for Children Boston)

  • Shannon L. Stott

    (Harvard Medical School and Massachusetts General Hospital
    Harvard Medical School)

  • Heidi Yeh

    (Massachusetts General Hospital)

  • Martin L. Yarmush

    (Harvard Medical School and Massachusetts General Hospital
    Shriners Hospitals for Children Boston
    Rutgers University)

  • Korkut Uygun

    (Harvard Medical School and Massachusetts General Hospital
    Shriners Hospitals for Children Boston)

  • Mehmet Toner

    (Harvard Medical School and Massachusetts General Hospital
    Shriners Hospitals for Children Boston)

Abstract

The limited preservation duration of organs has contributed to the shortage of organs for transplantation. Recently, a tripling of the storage duration was achieved with supercooling, which relies on temperatures between −4 and −6 °C. However, to achieve deeper metabolic stasis, lower temperatures are required. Inspired by freeze-tolerant animals, we entered high-subzero temperatures (−10 to −15 °C) using ice nucleators to control ice and cryoprotective agents (CPAs) to maintain an unfrozen liquid fraction. We present this approach, termed partial freezing, by testing gradual (un)loading and different CPAs, holding temperatures, and storage durations. Results indicate that propylene glycol outperforms glycerol and injury is largely influenced by storage temperatures. Subsequently, we demonstrate that machine perfusion enhancements improve the recovery of livers after freezing. Ultimately, livers that were partially frozen for 5-fold longer showed favorable outcomes as compared to viable controls, although frozen livers had lower cumulative bile and higher liver enzymes.

Suggested Citation

  • Shannon N. Tessier & Reinier J. de Vries & Casie A. Pendexter & Stephanie E. J. Cronin & Sinan Ozer & Ehab O. A. Hafiz & Siavash Raigani & Joao Paulo Oliveira-Costa & Benjamin T. Wilks & Manuela Loper, 2022. "Partial freezing of rat livers extends preservation time by 5-fold," Nature Communications, Nature, vol. 13(1), pages 1-13, December.
  • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-31490-2
    DOI: 10.1038/s41467-022-31490-2
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    References listed on IDEAS

    as
    1. David Nasralla & Constantin C. Coussios & Hynek Mergental & M. Zeeshan Akhtar & Andrew J. Butler & Carlo D. L. Ceresa & Virginia Chiocchia & Susan J. Dutton & Juan Carlos García-Valdecasas & Nigel Hea, 2018. "A randomized trial of normothermic preservation in liver transplantation," Nature, Nature, vol. 557(7703), pages 50-56, May.
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    Cited by:

    1. Zonghu Han & Joseph Sushil Rao & Lakshya Gangwar & Bat-Erdene Namsrai & Jacqueline L. Pasek-Allen & Michael L. Etheridge & Susan M. Wolf & Timothy L. Pruett & John C. Bischof & Erik B. Finger, 2023. "Vitrification and nanowarming enable long-term organ cryopreservation and life-sustaining kidney transplantation in a rat model," Nature Communications, Nature, vol. 14(1), pages 1-12, December.

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