TY - JOUR
T1 - Supercooling extends preservation time of human livers
AU - de Vries, Reinier J.
AU - Tessier, Shannon N.
AU - Banik, Peony D.
AU - Nagpal, Sonal
AU - Cronin, Stephanie E.J.
AU - Ozer, Sinan
AU - Hafiz, Ehab O.A.
AU - van Gulik, Thomas M.
AU - Yarmush, Martin L.
AU - Markmann, James F.
AU - Toner, Mehmet
AU - Yeh, Heidi
AU - Uygun, Korkut
PY - 2019/10/1
Y1 - 2019/10/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85072713100&partnerID=8YFLogxK
U2 - https://doi.org/10.1038/s41587-019-0223-y
DO - https://doi.org/10.1038/s41587-019-0223-y
M3 - Article
C2 - 31501557
VL - 37
SP - 1131
EP - 1136
JO - Nature biotechnology
JF - Nature biotechnology
SN - 1087-0156
IS - 10
ER -