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 () and Mehmet Toner ()
Additional contact information
Shannon N. Tessier: Harvard Medical School and Massachusetts General Hospital
Reinier J. de Vries: Harvard Medical School and Massachusetts General Hospital
Casie A. Pendexter: Harvard Medical School and Massachusetts General Hospital
Stephanie E. J. Cronin: Harvard Medical School and Massachusetts General Hospital
Sinan Ozer: Harvard Medical School and Massachusetts General Hospital
Ehab O. A. Hafiz: Theodor Bilharz Research Institute
Siavash Raigani: Shriners Hospitals for Children Boston
Joao Paulo Oliveira-Costa: Harvard Medical School and Massachusetts General Hospital
Benjamin T. Wilks: Harvard Medical School and Massachusetts General Hospital
Manuela Lopera Higuita: Harvard Medical School and Massachusetts General Hospital
Thomas M. van Gulik: University of Amsterdam
Osman Berk Usta: Harvard Medical School and Massachusetts General Hospital
Shannon L. Stott: Harvard Medical School and Massachusetts General Hospital
Heidi Yeh: Massachusetts General Hospital
Martin L. Yarmush: Harvard Medical School and Massachusetts General Hospital
Korkut Uygun: Harvard Medical School and Massachusetts General Hospital
Mehmet Toner: Harvard Medical School and Massachusetts General Hospital

Nature Communications, 2022, vol. 13, issue 1, 1-13

Abstract: 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.

Date: 2022
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DOI: 10.1038/s41467-022-31490-2

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