Evidence map›Paper›PMID 32433625›Full record

ArticleNature protocols2020

Subzero non-frozen preservation of human livers in the supercooled state.

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 and 3 more

Abstract read
In one paragraph

Article in Nature protocols, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.

0numbers the graph read from it
0cells of the map it votes in
30citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

30 citing papers in PubMed.

  1. Article
  2. Article
  3. Cryopreservation of biological materials: applications and economic perspectives.In vitro cellular & developmental biology. Animal · 2026
    Review
  4. Review
  5. Review
  6. Article
  7. Article
  8. Article
  9. Article
  10. Article
  11. Article
  12. Article
  13. Review
  14. Machine Perfusion Enables 24-h Preservation of Vascularized Composite Allografts in a Swine Model of Allotransplantation.Transplant international : official journal of the European Society for Organ Transplantation · 2024
    Article
  15. Supercooled preservation of cultured primary rat hepatocyte monolayers.Frontiers in bioengineering and biotechnology · 2024
    Article
  16. Article
  17. Zebrafish as a high throughput model for organ preservation and transplantation research.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2023
    Article
  18. Isochoric Supercooling Organ Preservation System.Bioengineering (Basel, Switzerland) · 2023
    Article
  19. Article
  20. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

13 authors.

Reinier J de VriesCenter for Engineering in Medicine, Harvard Medical School & Massachusetts General Hospital, Boston, MA, USA.ORCID http://orcid.org/0000-0002-4741-0686
Shannon N TessierCenter for Engineering in Medicine, Harvard Medical School & Massachusetts General Hospital, Boston, MA, USA.
Peony D BanikCenter for Engineering in Medicine, Harvard Medical School & Massachusetts General Hospital, Boston, MA, USA.
Sonal NagpalCenter for Engineering in Medicine, Harvard Medical School & Massachusetts General Hospital, Boston, MA, USA.
Stephanie E J CroninCenter for Engineering in Medicine, Harvard Medical School & Massachusetts General Hospital, Boston, MA, USA.
Sinan OzerCenter for Engineering in Medicine, Harvard Medical School & Massachusetts General Hospital, Boston, MA, USA.
Ehab O A HafizCenter for Engineering in Medicine, Harvard Medical School & Massachusetts General Hospital, Boston, MA, USA.ORCID http://orcid.org/0000-0002-1551-4309
Thomas M van GulikDepartment of Surgery, Amsterdam University Medical Centers-location AMC, University of Amsterdam, Amsterdam, the Netherlands.
Martin L YarmushCenter for Engineering in Medicine, Harvard Medical School & Massachusetts General Hospital, Boston, MA, USA.
James F MarkmannCenter for Transplant Sciences, Massachusetts General Hospital, Boston, MA, USA.
Mehmet TonerCenter for Engineering in Medicine, Harvard Medical School & Massachusetts General Hospital, Boston, MA, USA.
Heidi YehCenter for Transplant Sciences, Massachusetts General Hospital, Boston, MA, USA.
Korkut UygunCenter for Engineering in Medicine, Harvard Medical School & Massachusetts General Hospital, Boston, MA, USA. kuygun@mgh.harvard.edu.ORCID http://orcid.org/0000-0003-2088-7860

Funding

High subzero preservation of liver for transplantationR01DK114506 · NIDDK · MASSACHUSETTS GENERAL HOSPITAL · PI TONER, MEHMET, UYGUN, KORKUT · 2017 to 2025
$4.4M
Metabolic Modeling for Cadaveric Organ ResuscitationR01DK096075 · NIDDK · MASSACHUSETTS GENERAL HOSPITAL · PI UYGUN, KORKUT, YEH, HEIDI · 2012 to 2022
$3.9M
Expanding the Liver Transplant Organ Pool through Ex Vivo Liver PerfusionR01DK107875 · NIDDK · MASSACHUSETTS GENERAL HOSPITAL · PI MARKMANN, JAMES FRANCIS, UYGUN, KORKUT · 2016 to 2020
$2.8M
High subzero heart preservation: from zebrafish to mammalsR01HL157803 · NHLBI · MASSACHUSETTS GENERAL HOSPITAL · PI Shannon Noella Tessier · 2021 to 2026
$2.8M
Whole heart suspended animation: leveraging the zebrafish to solve the organ shortageR00HL143149 · NHLBI · MASSACHUSETTS GENERAL HOSPITAL · PI TESSIER, SHANNON NOELLA · 2021 to 2023
$747k
Equilibrium sub-cooling for non-frozen banking of human liversR21EB023031 · NIBIB · SYLVATICA BIOTECH, INC. · PI TAYLOR, MICHAEL JOHN · 2016 to 2017
$571k
Whole heart suspended animation: leveraging the zebrafish to solve the organ shortageK99HL143149 · NHLBI · MASSACHUSETTS GENERAL HOSPITAL · PI TESSIER, SHANNON NOELLA · 2019 to 2020
$215k
NHLBI NIH HHS K99 HL143149NHLBI NIH HHS R00 HL143149NHLBI NIH HHS R01 HL157803NIBIB NIH HHS R21 EB023031NIDDK NIH HHS R01 DK096075NIDDK NIH HHS R01 DK107875NIDDK NIH HHS R01 DK114506U.S. Department of Defense (United States Department of Defense) RTRP W81XWH-17-1-0680U.S. Department of Health & Human Services | NIH | National Institute of Diabetes and Digestive and Kidney Diseases (National Institute of Diabetes & Digestive & Kidney Diseases) R01DK096075U.S. Department of Health & Human Services | NIH | National Institute of Diabetes and Digestive and Kidney Diseases (National Institute of Diabetes & Digestive & Kidney Diseases) R01DK107875U.S. Department of Health & Human Services | NIH | National Institute of Diabetes and Digestive and Kidney Diseases (National Institute of Diabetes & Digestive & Kidney Diseases) R01DK114506
6 · The paper itself

Abstract

Preservation of human organs at subzero temperatures has been an elusive goal for decades. The major complication hindering successful subzero preservation is the formation of ice at temperatures below freezing. Supercooling, or subzero non-freezing, preservation completely avoids ice formation at subzero temperatures. We previously showed that rat livers can be viably preserved three times longer by supercooling as compared to hypothermic preservation at +4 °C. Scalability of supercooling preservation to human organs was intrinsically limited because of volume-dependent stochastic ice formation at subzero temperatures. However, we recently adapted the rat preservation approach so it could be applied to larger organs. Here, we describe a supercooling protocol that averts freezing of human livers by minimizing air-liquid interfaces as favorable sites of ice nucleation and uses preconditioning with cryoprotective agents to depress the freezing point of the liver tissue. Human livers are homogeneously preconditioned during multiple machine perfusion stages at different temperatures. Including preparation, the protocol takes 31 h to complete. Using this protocol, human livers can be stored free of ice at -4 °C, which substantially extends the ex vivo life of the organ. To our knowledge, this is the first detailed protocol describing how to perform subzero preservation of human organs.

Indexed as

Cold TemperatureCryoprotective AgentsEquipment DesignFreezingHumansIceLiverOrgan PreservationPerfusionCryoprotective AgentsIce

Identifiers

PMID32433625
PMCPMC8568322

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.