Technical Report | Published:

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

Nature Medicine volume 20, pages 790793 (2014) | Download Citation

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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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.

Author information

Affiliations

  1. Center for Engineering in Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA.

    • Tim A Berendsen
    • , Bote G Bruinsma
    • , Catheleyne F Puts
    • , Nima Saeidi
    • , O Berk Usta
    • , Basak E Uygun
    • , Maria-Louisa Izamis
    • , Mehmet Toner
    • , Martin L Yarmush
    •  & Korkut Uygun
  2. Department of Surgery, University Medical Center, Utrecht, the Netherlands.

    • Tim A Berendsen
  3. Department of Biomedical Engineering, Rutgers University, Piscataway, New Jersey, USA.

    • Martin L Yarmush

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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.

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.

Corresponding authors

Correspondence to Martin L Yarmush or Korkut Uygun.

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DOI

https://doi.org/10.1038/nm.3588

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