Evidence map›Paper›PMID 42414621›Full record

ArticleNature medicine2026

Longitudinal multiomics profiling of extracorporeal cross-circulation with pig liver xenografts in human decedents.

Qian Guo, Chan Wang, Vincent Mauduit, Alexey Stukalov, Maede Mohebnasab, Alex Sagar, Susanna Vikman, Simon H Williams, Berk Maden, Tal Eitan and 36 more

Abstract read
PubMed Publisher
In one paragraph

Article in Nature medicine, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing 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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

46 authors.

Qian GuoNYU Langone Transplant Institute, NYU Langone Health, New York, NY, USA.ORCID http://orcid.org/0000-0002-8622-8553
Chan WangNYU Langone Transplant Institute, NYU Langone Health, New York, NY, USA.ORCID http://orcid.org/0000-0002-1718-5414
Vincent MauduitNYU Langone Transplant Institute, NYU Langone Health, New York, NY, USA.
Alexey StukalovSeer Inc., Redwood City, CA, USA.ORCID http://orcid.org/0000-0002-4981-8124
Maede MohebnasabNYU Langone Transplant Institute, NYU Langone Health, New York, NY, USA.ORCID http://orcid.org/0000-0001-6623-9514
Alex SagarNuffield Department of Surgical Sciences, University of Oxford, Oxford, UK.
Susanna VikmanNYU Langone Transplant Institute, NYU Langone Health, New York, NY, USA.
Simon H WilliamsNYU Langone Transplant Institute, NYU Langone Health, New York, NY, USA.
Berk MadenNYU Langone Transplant Institute, NYU Langone Health, New York, NY, USA.ORCID http://orcid.org/0009-0005-8941-7367
Tal EitanNYU Langone Transplant Institute, NYU Langone Health, New York, NY, USA.ORCID http://orcid.org/0000-0002-0811-6871
Krista BaroneNYU Langone Transplant Institute, NYU Langone Health, New York, NY, USA.
Jennifer D MotterNYU Langone Transplant Institute, NYU Langone Health, New York, NY, USA.
Alexa K DowdellEarle A. Chiles Research Institute, Providence Cancer Institute, Portland, OR, USA.ORCID http://orcid.org/0000-0003-4866-6293
Fred L RobinsonEarle A. Chiles Research Institute, Providence Cancer Institute, Portland, OR, USA.
Cyrille Guillot-TantayNYU Langone Transplant Institute, NYU Langone Health, New York, NY, USA.
Zasha ZayasNYU Langone Transplant Institute, NYU Langone Health, New York, NY, USA.
Justin P LittleNYU Langone Transplant Institute, NYU Langone Health, New York, NY, USA.
Kleio-Maria VerrouNYU Langone Transplant Institute, NYU Langone Health, New York, NY, USA.
Ángel Gálvez-MercháneGenesis, Cambridge, MA, USA.ORCID http://orcid.org/0000-0001-7420-8697
Peng GuoNYU Langone Transplant Institute, NYU Langone Health, New York, NY, USA.
Kiana MoiNYU Langone Transplant Institute, NYU Langone Health, New York, NY, USA.
Emmry StimsonNYU Langone Transplant Institute, NYU Langone Health, New York, NY, USA.ORCID http://orcid.org/0009-0000-9443-8721
Hui GaoNYU Langone Transplant Institute, NYU Langone Health, New York, NY, USA.
Diana ArgibayNYU Langone Transplant Institute, NYU Langone Health, New York, NY, USA.
Leah WuNYU Langone Transplant Institute, NYU Langone Health, New York, NY, USA.
Austin G HolmesNYU Langone Transplant Institute, NYU Langone Health, New York, NY, USA.
Alexandra Q BartlettEarle A. Chiles Research Institute, Providence Cancer Institute, Portland, OR, USA.
Dong XinDivision of Transplant Surgery, Department of Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Hannah FuteranDivision of Transplant Surgery, Department of Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Serafim BatzoglouSeer Inc., Redwood City, CA, USA.
Shreyas JoshiNYU Langone Transplant Institute, NYU Langone Health, New York, NY, USA.
Mercy RophinaNYU Langone Transplant Institute, NYU Langone Health, New York, NY, USA.
Francesca ZanoniNYU Langone Transplant Institute, NYU Langone Health, New York, NY, USA.
Mohamed A ElzawahryNuffield Department of Surgical Sciences, University of Oxford, Oxford, UK.ORCID http://orcid.org/0000-0001-5300-912X
John I FallonNuffield Department of Surgical Sciences, University of Oxford, Oxford, UK.ORCID http://orcid.org/0000-0002-8644-9380
Syed Hussain AbbasNuffield Department of Surgical Sciences, University of Oxford, Oxford, UK.
Kim M OlthoffDivision of Transplant Surgery, Department of Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.ORCID http://orcid.org/0000-0001-5181-7502
Charles S AbramsDepartment of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Sagar ChhangawalaeGenesis, Cambridge, MA, USA.
Adam GriesemerNYU Langone Transplant Institute, NYU Langone Health, New York, NY, USA.ORCID http://orcid.org/0000-0003-4894-2024
Peter FriendNuffield Department of Surgical Sciences, University of Oxford, Oxford, UK.ORCID http://orcid.org/0000-0003-0841-9685
Asim SiddiquiSeer Inc., Redwood City, CA, USA.ORCID http://orcid.org/0000-0002-0359-2334
Eloi SchmauchNYU Langone Transplant Institute, NYU Langone Health, New York, NY, USA.
Brian D PieningEarle A. Chiles Research Institute, Providence Cancer Institute, Portland, OR, USA.ORCID http://orcid.org/0000-0002-2683-8157
Abraham ShakedDivision of Transplant Surgery, Department of Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.ORCID http://orcid.org/0000-0002-2162-095X
Brendan J KeatingNYU Langone Transplant Institute, NYU Langone Health, New York, NY, USA. brendan.keating@nyulangone.org.ORCID http://orcid.org/0000-0002-3320-3723

Funding

Project 2U19AI191396 · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · 2025 to 2025
$2.9M
Immunobiology and Physiology of Liver xenograft in the DecedentU01AI191397 · UNIVERSITY OF PENNSYLVANIA · 2025 to 2025
$1.3M
NIAID NIH HHS U01 AI191397NIAID NIH HHS U19 AI191396
6 · The paper itself

Abstract

Extracorporeal liver cross-circulation (ELC) using gene-edited porcine liver xenografts offers a potential bridge therapy for liver failure. We previously performed five ELC procedures in four brain-dead human decedents, during which the recipients developed severe thrombocytopenia. The porcine liver xenografts maintained their parenchymal structure, with immune cell infiltration and detectable IgM deposition on endothelial cells. Here, to investigate the underlying host-xenograft interactions, we performed longitudinal proteomic, lipidomic and metabolomic profiling of 64 blood samples, alongside spatial transcriptomics and histology of 25 porcine liver xenograft and 3 native human liver biopsies. Spatial transcriptomic analysis revealed progressive infiltration of human immune cells (predominantly inflammatory macrophages and neutrophils) in the xenografts, concurrent with the loss of porcine Kupffer-like macrophages and T cells. Distinct human and porcine complement dynamics were observed, with suppressed human but elevated porcine complement levels, accompanied by increased levels of porcine acute-phase proteins and coagulation factors. Moreover, multiomics analyses identified candidate cellular and molecular factors associated with thrombocytopenia. Human platelets colocalized with activated porcine endothelial cells, which showed increasing porcine vWF expression over time, as well as with immune cells (primarily macrophages and neutrophils) and hepatocytes in the xenografts. Integrative analyses indicated that ELC procedures provided hepatic support for apolipoprotein synthesis, bilirubin clearance, energy metabolism and detoxification, although circulating lipid levels remained low under anhepatic conditions. Collectively, these findings yield insights into the complex interplay between human and xenograft systems during ELC and inform strategies to improve liver xenograft biocompatibility for clinical translation.

Indexed as

HeterograftsLiverLiver TransplantationAnimalsFemaleHumansMacrophagesMaleMetabolomicsMultiomicsProteomicsSwineThrombocytopeniaTransplantation, Heterologous

Identifiers

PMID42414621

What Socratic holds

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Registered trials

None linked

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 Socratic graph.