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Supercooling enables long-term transplantation survival following 4 days of liver preservation

Abstract

The realization of long-term human organ preservation will have groundbreaking effects on the current practice of transplantation. Herein we present a new technique based on subzero nonfreezing preservation and extracorporeal machine perfusion that allows transplantation of rat livers preserved for up to four days, thereby tripling the viable preservation duration.

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Figure 1: Transplantation of supercooled livers.
Figure 2: Subnormothermic machine perfusion recovery and histology.

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Acknowledgements

Funding from the US National Institutes of Health (grants R01EB008678, R01DK096075, R01DK084053, R00DK080942, R00DK088962 and F32 DK095558) and the Shriners Hospitals for Children is gratefully acknowledged.

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Authors

Contributions

T.A.B., B.G.B., M.-L.I., O.B.U., B.E.U., M.T., M.L.Y. and K.U. conceived and designed the study; T.A.B., B.G.B., C.F.P. and N.S. performed data acquisition; T.A.B., B.G.B., M.-L.I., M.L.Y. and K.U. analyzed and interpreted data; T.A.B. and B.G.B. performed rat liver procurement and transplantation; T.A.B., B.G.B. and M.-L.I. designed and constructed the supercooling device and container; T.A.B., B.G.B. and K.U. wrote the manuscript; T.A.B., B.G.B., C.F.P., N.S., O.B.U., B.E.U., M.-L.I., M.T., M.L.Y. and K.U. participated in critical revision of the manuscript for intellectual content; T.A.B., B.G.B. and K.U. performed statistical analysis; and M.L.Y. and K.U. obtained funding. All authors contributed to the preparation of the manuscript.

Corresponding authors

Correspondence to Martin L Yarmush or Korkut Uygun.

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Competing interests

M.L.I., B.E.U., K.U. and M.L.Y. are inventors on a pending international patent application that involves some of the perfusion technology used in this work (WO/2011/002926); T.A.B., M.L.I., B.E.U., M.L.Y. and K.U. are inventors on a pending international patent application that describes the supercooling protocol employed in this work (WO/2011/35223); and B.G.B., M.L.I. and K.U. have a provisional patent application related to this work that describes scale-up of the perfusion protocol to human livers. K.U. has a financial interest in Organ Solutions LLC, a company focused on developing organ preservation technology. K.U.'s interests are managed by the Massachusetts General Hospital and Partners HealthCare in accordance with their conflict-of-interest policies.

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Berendsen, T., Bruinsma, B., Puts, C. et al. Supercooling enables long-term transplantation survival following 4 days of liver preservation. Nat Med 20, 790–793 (2014). https://doi.org/10.1038/nm.3588

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