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Nature Medicine

Physiology and immunology of a pig-to-human decedent kidney xenotransplant

  • November 13, 2025
  • Megan Sykes, et al., Columbia University
Product:
Inflammation Panel 250
Topic:
Immunology
Disease Area:
Xenotransplant
Sample Type:
Serum
Back to Publications​
  • November 13, 2025
  • Megan Sykes, et al., Columbia University
Topic/Product:
Inflammation Panel 250
Disease Area:
Xenotransplant
Sample Type:
Serum

Abstract

Xenotransplantation of genetically modified pig kidneys offers a solution to the scarcity of organs for patients with end stage renal disease1. Here we performed a pig kidney thymic autograft transplantation from an α1,3-galactosyltransferase knockout (GGTA1-knockout, GTKO) pig into a nephrectomized brain-dead human using clinically approved immunosuppression, without CD40 blockade or additional genetic modification, and somatically supported the decendent for a pre-planned 61-day study. Haemodynamic and electrolyte stability and dialysis independence were achieved. Biopsies from post-operative day (POD) 10 revealed glomerular IgM and IgA deposition, activation of early complement components and mesangiolysis with stable renal function without proteinuria, a phenotype that is not seen in allotransplantation. On POD33, an abrupt increase in serum creatinine was associated with antibody-mediated rejection and increased donor-specific IgG. Plasma exchange, complement C3 and C3b inhibition, and rabbit anti-thymocyte globulin (rATG) completely reversed xenograft rejection. After the xenotransplant, pre-existing donor-reactive T cell clones expanded progressively in the circulation and acquired an effector transcriptional profile, and were detected in the POD33 rejecting xenograft prior to rATG treatment. This study presents long-term physiological, immunological and infectious disease monitoring of a pig-to-human kidney xenotransplant and indicates that pre-existing xenoreactive T cells and induced antibodies to unknown epitopes present a major challenge, despite significant immunosuppression. It also demonstrates that a minimally gene-edited pig kidney can support long-term life-sustaining physiological functions in a human.

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Authors & Affiliations

Robert A. Montgomery¹, Jeffrey M. Stern¹, Farshid Fathi², Nathan Suek², Jacqueline I. Kim³, Karen Khalil¹, Benjamin Vermette², Vasishta S. Tatapudi¹, Aprajita Mattoo¹, Edward Y. Skolnik⁴⁵, Ian S. Jaffe³, Imad Aljabban¹², Tal Eitan¹, Shivani Bisen⁶, Elaina P. Weldon¹, Valentin Goutaudier⁷, Erwan Morgand⁷, Fariza Mezine⁷, Alessia Giarraputo⁷, Idris Boudhabhay⁸, Patrick Bruneval⁷, Aurelie Sannier⁷, Kevin Breen²⁹, Yasmeen S. Saad², Constanza Bay Muntnich², Simon H. Williams¹¹, Weimin Zhang¹¹, Larisa Kagermazova¹¹, Eloi Schmauch¹, Chandra Goparaju¹², Rebecca Dieter¹, Nikki Lawson¹, Amy Dandro¹³, Ana Laura Fazio-Kroll¹³, Lars Burdorf¹³, David Ayares¹³, Marc Lorber¹⁴, Dorry Segev³¹⁵, Nicole Ali¹, David S. Goldfarb⁴¹⁶, Victoria Costa¹⁷, Timothy Hilbert¹⁷, Sapna A. Mehta¹, Ramin S. Herati⁴, Harvey I. Pass¹², Ming Wu¹⁷, Jef D. Boeke¹⁸¹⁹, Brendan Keating³, Massimo Mangiola¹¹⁷, Philip M. Sommer¹²⁰, Alexandre Loupy⁸, Adam Griesemer¹, and Megan Sykes²²¹

¹ New York University Langone Transplant Institute, New York, NY, USA
² Columbia Center for Translational Immunology, Department of Medicine, Columbia University, New York, NY, USA
³ Department of Surgery, New York University Grossman School of Medicine, New York, NY, USA
⁴ Department of Medicine, New York University Grossman School of Medicine, New York, NY, USA
⁵ Department of Cell Biology, New York University Grossman School of Medicine, New York, NY, USA
⁶ New York University Grossman School of Medicine, New York University, New York, NY, USA
⁷ Université Paris Cité, INSERM U970, Paris Institute for Transplantation and Organ Regeneration (PITOR), Paris, France
⁸ Team Inflammation Complement and Cancer, Centre de Recherche des Cordeliers, INSERM, Sorbonne Université, Université Paris Cité, Paris, France
⁹ Oxford University Hospitals NHS Foundation Trust, Oxford, UK
¹⁰ Institute for Systems Genetics, New York University Grossman School of Medicine, New York, NY, USA
¹¹ Department of Cardiothoracic Surgery, New York University Langone Health, New York, NY, USA
¹² Department of Population Health, New York University Grossman School of Medicine, New York, NY, USA
¹³ Revivicor, Blacksburg, VA, USA
¹⁴ United Therapeutics Corporation, Silver Spring, MD, USA
¹⁵ Department of Neuroscience and Physiology, New York University Grossman School of Medicine, New York, NY, USA
¹⁶ Department of Pathology, New York University Langone Health, New York, NY, USA
¹⁷ Department of Biochemistry and Molecular Pharmacology, New York University Grossman School of Medicine, New York, NY, USA
¹⁸ Department of Biomedical Engineering, NYU Tandon School of Engineering, Brooklyn, NY, USA
¹⁹ Department of Anesthesiology, Perioperative Care, and Pain Medicine, New York University Grossman School of Medicine, New York, NY, USA
²⁰ Department of Microbiology and Immunology, Columbia University, New York, NY, USA
²¹ Department of Surgery, Columbia University, New York, NY, USA

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Steve Williams, MD, PhD

CSO

Dr. Willams serves as the company’s Chief Scientific Officer. He was previously Chief Medical Officer at Standard Biotools and at SomaLogic where he pioneered the discipline for discovery and validation of predictive, diagnostic and prognostic models using machine-learning applied to large-plex proteomics. 20 such tests were used for drug characterization, safety and efficacy when incorporated in clinical drug trials at Pharma/Biotech and 17 different multivariate tests were validated and translated into regulated healthcare uses. Prior to SomaLogic, Dr. Williams was at Pfizer in the UK and the USA as a clinical triallist in Translational Medicine, and subsequently as VP, Global Clinical Technology. He sat on the National Advisory Council for the National Institute of Biomedical Imaging and Bioengineering, the Executive Committee for the FNIH Biomarkers Consortium, and worked with FDA and PhRMA on developing evidentiary standards for biomarker qualification. Dr. William’s medical training was in London, at Charing Cross and Westminster Medical School, followed by a PhD in medicine/physiology at the same institution and training in Radiology at the University of Newcastle Upon Tyne. Steve is co-inventor on 26 proteomics patents and author/coauthor on multiple foundational proteomics manuscripts.

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Justin McAnear

CFO

Mr. McAnear serves as the company’s Chief Financial Officer. He brings over 25 years of operational and financial leadership experience across various sectors and was instrumental in taking 10x Genomics public in 2019, serving as its CFO for over five years. Mr. McAnear served for over 3 years as Tesla’s VP of Worldwide Finance and Operations, supporting landmark initiatives such as the Model X and Model 3 launches and Solar City acquisition.  He also held various roles at Apple and J&J earlier in his career and served as a naval officer and aviator for over 9 years.