Supercooling extends preservation time of human livers

Reinier J. de Vries, Shannon N. Tessier, Peony D. Banik, Sonal Nagpal, Stephanie E.J. Cronin, Sinan Ozer, Ehab O.A. Hafiz, Thomas M. van Gulik, Martin L. Yarmush, James F. Markmann, Mehmet Toner, Heidi Yeh, Korkut Uygun

Research output: Contribution to JournalArticleAcademicpeer-review

83 Citations (Scopus)

Abstract

The inability to preserve vascular organs beyond several hours contributes to the scarcity of organs for transplantation1,2. Standard hypothermic preservation at +4 °C (refs. 1,3) limits liver preservation to less than 12 h. Our group previously showed that supercooled ice-free storage at –6 °C can extend viable preservation of rat livers4,5 However, scaling supercooling preservation to human organs is intrinsically limited because of volume-dependent stochastic ice formation. Here, we describe an improved supercooling protocol that averts freezing of human livers by minimizing favorable sites of ice nucleation and homogeneous preconditioning with protective agents during machine perfusion. We show that human livers can be stored at –4 °C with supercooling followed by subnormothermic machine perfusion, effectively extending the ex vivo life of the organ by 27 h. We show that viability of livers before and after supercooling is unchanged, and that after supercooling livers can withstand the stress of simulated transplantation by ex vivo normothermic reperfusion with blood.

Original languageEnglish
Pages (from-to)1131-1136
Number of pages6
JournalNature Biotechnology
Volume37
Issue number10
DOIs
Publication statusPublished - 1 Oct 2019

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