Evidence map›Paper›PMID 37393920›Full record

ArticleLancet (London, England)2023

Graft dysfunction in compassionate use of genetically engineered pig-to-human cardiac xenotransplantation: a case report.

Muhammad M Mohiuddin, Avneesh K Singh, Linda Scobie, Corbin E Goerlich, Alison Grazioli, Kapil Saharia, Claire Crossan, Allen Burke, Cinthia Drachenberg, Cihan Oguz and 17 more

Open access · greenAbstract readCase Reports
PubMed Full text at PMC Publisher
In one paragraph

Article in Lancet (London, England), 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 136 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
136citing papers in PubMed, 1 pooled it
67.3field-weighted citation impact, top 1% of its field
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

136 citing papers in PubMed, 1 synthesis or guideline pooled it, 213 citations in OpenAlex.

  1. Pooled it
  2. Review
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  5. Review
  6. Review
  7. Article
  8. Review
  9. The making of cells and organs in xenogeneic animal bioreactor.Signal transduction and targeted therapy · 2026
    Review
  10. Review
  11. Article
  12. Review
  13. Large animal models of right heart failure due to pulmonary hypertension: a bridge to translational success.European respiratory review : an official journal of the European Respiratory Society · 2026
    Review
  14. Article
  15. Article
  16. Gene-edited pig cardiac xenotransplantation as a bridge to allotransplantation in infants: Progress in a pig-to-baboon model.American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons · 2026
    Article
  17. Complement activation in kidney transplantation.Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association · 2026
    Review
  18. Review
  19. Transgenic expression of human CD47 on pig cells provides only partial protection against human macrophage-mediated destruction in human immune system mice.American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons · 2026
    Article
  20. Article

76 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

27 authors at 5 institutions in 2 countries.

Muhammad M MohiuddinProgram in Cardiac Xenotransplantation, Department of Surgery, University of Maryland School of Medicine, Baltimore, MD, USA. Electronic address: mmohiuddin@som.umaryland.edu.
Avneesh K SinghProgram in Cardiac Xenotransplantation, Department of Surgery, University of Maryland School of Medicine, Baltimore, MD, USA.
Linda ScobieDepartment of Biological and Biomedical Sciences, Glasgow Caledonian University, Glasgow, UK.
Corbin E GoerlichProgram in Cardiac Xenotransplantation, Department of Surgery, University of Maryland School of Medicine, Baltimore, MD, USA.
Alison GrazioliCardiac Surgery Intensive Care Unit, University of Maryland Medical Center, Baltimore, MD, USA.
Kapil SahariaInstitute of Human Virology, Division of Infectious Disease, University of Maryland School of Medicine, Baltimore, MD, USA.
Claire CrossanDepartment of Biological and Biomedical Sciences, Glasgow Caledonian University, Glasgow, UK.
Allen BurkeDepartment of Pathology, University of Maryland Medical Center, Baltimore, MD, USA.
Cinthia DrachenbergDepartment of Pathology, University of Maryland Medical Center, Baltimore, MD, USA.
Cihan OguzIntegrated Data Sciences Section, Research Technologies Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
Tianshu ZhangProgram in Cardiac Xenotransplantation, Department of Surgery, University of Maryland School of Medicine, Baltimore, MD, USA.
Billeta LewisProgram in Cardiac Xenotransplantation, Department of Surgery, University of Maryland School of Medicine, Baltimore, MD, USA.
Alena HershfeldProgram in Cardiac Xenotransplantation, Department of Surgery, University of Maryland School of Medicine, Baltimore, MD, USA.
Faith SentzProgram in Cardiac Xenotransplantation, Department of Surgery, University of Maryland School of Medicine, Baltimore, MD, USA.
Ivan TatarovProgram in Cardiac Xenotransplantation, Department of Surgery, University of Maryland School of Medicine, Baltimore, MD, USA.
Sarah MuddProgram in Cardiac Xenotransplantation, Department of Surgery, University of Maryland School of Medicine, Baltimore, MD, USA.
Gheorghe BraileanuProgram in Cardiac Xenotransplantation, Department of Surgery, University of Maryland School of Medicine, Baltimore, MD, USA.
Kathryn RiceDepartment of Pathology, University of Maryland Medical Center, Baltimore, MD, USA.
John F PaoliniKiniksa Pharmaceuticals, Lexington, MA, USA.
Kent BondensgaardKiniksa Pharmaceuticals, Lexington, MA, USA.
Todd VaughtRevivicor, Blacksburg, VA, USA.
Kasinath KuraviRevivicor, Blacksburg, VA, USA.
Lori SorrellsRevivicor, Blacksburg, VA, USA.
Amy DandroRevivicor, Blacksburg, VA, USA.
David AyaresRevivicor, Blacksburg, VA, USA.
Christine LauProgram in Cardiac Xenotransplantation, Department of Surgery, University of Maryland School of Medicine, Baltimore, MD, USA.
Bartley P GriffithProgram in Cardiac Xenotransplantation, Department of Surgery, University of Maryland School of Medicine, Baltimore, MD, USA.
University of Maryland, Baltimore · USUniversity of Maryland Medical Center · USGlasgow Caledonian University · GBSynta Pharmaceuticals (United States) · USNational Institutes of Health · US

Funding

Prolonging life-supported pig kidney and heart graft survival in baboons by suppressing inflammationU19AI090959 · NIAID · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI MOHIUDDIN, MUHAMMAD M · 2010 to 2024
$26.3M
NIAID NIH HHS U19 AI090959
6 · The paper itself

Abstract

backgroundA genetically engineered pig cardiac xenotransplantation was done on Jan 7, 2022, in a non-ambulatory male patient, aged 57 years, with end-stage heart failure, and on veno-arterial extracorporeal membrane oxygenation support, who was ineligible for an allograft. This report details our current understanding of factors important to the xenotransplantation outcome.

methodsPhysiological and biochemical parameters critical for the care of all heart transplant recipients were collected in extensive clinical monitoring in an intensive care unit. To ascertain the cause of xenograft dysfunction, we did extensive immunological and histopathological studies, including electron microscopy and quantification of porcine cytomegalovirus or porcine roseolovirus (PCMV/PRV) in the xenograft, recipient cells, and tissue by DNA PCR and RNA transcription. We performed intravenous immunoglobulin (IVIG) binding to donor cells and single-cell RNA sequencing of peripheral blood mononuclear cells.

findingsAfter successful xenotransplantation, the graft functioned well on echocardiography and sustained cardiovascular and other organ systems functions until postoperative day 47 when diastolic heart failure occurred. At postoperative day 50, the endomyocardial biopsy revealed damaged capillaries with interstitial oedema, red cell extravasation, rare thrombotic microangiopathy, and complement deposition. Increased anti-pig xenoantibodies, mainly IgG, were detected after IVIG administration for hypogammaglobulinaemia and during the first plasma exchange. Endomyocardial biopsy on postoperative day 56 showed fibrotic changes consistent with progressive myocardial stiffness. Microbial cell-free DNA testing indicated increasing titres of PCMV/PRV cell-free DNA. Post-mortem single-cell RNA sequencing showed overlapping causes.

interpretationHyperacute rejection was avoided. We identified potential mediators of the observed endothelial injury. First, widespread endothelial injury indicates antibody-mediated rejection. Second, IVIG bound strongly to donor endothelium, possibly causing immune activation. Finally, reactivation and replication of latent PCMV/PRV in the xenograft possibly initiated a damaging inflammatory response. The findings point to specific measures to improve xenotransplant outcomes in the future.

fundingThe University of Maryland School of Medicine, and the University of Maryland Medical Center.

Indexed as

Heart FailureHeart TransplantationAnimalsCompassionate Use TrialsGraft RejectionHeartHumansImmunoglobulins, IntravenousLeukocytes, MononuclearMaleMiddle AgedSwineTransplantation, HeterologousImmunoglobulins, Intravenous

Identifiers

PMID37393920
PMCPMC10552929
OpenAlexW4382517975

What OpenQuestion holds

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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.