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

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 Lopera Higuita, Thomas M. van Gulik, Osman Berk Usta, Shannon L. Stott, Heidi Yeh, Martin L. Yarmush, Korkut Uygun, Mehmet Toner

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Article number4008
JournalNature communications
Volume13
Issue number1
DOIs
StatePublished - Dec 2022

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • General
  • Physics and Astronomy(all)

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