Genetically Modified Porcine-to-Human Cardiac Xenotransplantation

Paper

Abstract

A 57-year-old man with nonischemic cardiomyopathy who was dependent on venoarterial extracorporeal membrane oxygenation (ECMO) and was not a candidate for standard therapeutics, including a traditional allograft, received a heart from a genetically modified pig source animal that had 10 individual gene edits. Immunosuppression was based on CD40 blockade. The patient was weaned from ECMO, and the xenograft functioned normally without apparent rejection. Sudden diastolic thickening and failure of the xenograft occurred on day 49 after transplantation, and life support was withdrawn on day 60. On autopsy, the xenograft was found to be edematous, having nearly doubled in weight. Histologic examination revealed scattered myocyte necrosis, interstitial edema, and red-cell extravasation, without evidence of microvascular thrombosis - findings that were not consistent with typical rejection. Studies are under way to identify the mechanisms responsible for these changes. (Funded by the University of Maryland Medical Center and School of Medicine.).

Analysis

Paper intelligence

Summary

A groundbreaking xenotransplantation of a genetically modified pig heart into a human patient demonstrated initial success and normal function before succumbing to unexplained graft failure.

Key findings

Successful xenograft function and weaning from ECMO.
Absence of typical rejection or microvascular thrombosis.
Sudden diastolic thickening and graft failure on day 49.
Edematous xenograft with myocyte necrosis and interstitial edema at autopsy.

Methods

Transplantation of a pig heart with 10 gene edits.
Immunosuppression using CD40 blockade.
Post-transplant monitoring and autopsy.

Limitations

Unidentified mechanisms of xenograft failure.
Single patient case study.

Applications

Potential treatment for end-stage heart failure.
Advancement of xenotransplantation research.

Confidence100%

Discovery

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Source record

Publication metadata

Authors: Bartley P. Griffith; Corbin E. Goerlich; Avneesh K. Singh; Martine Rothblatt; Christine L. Lau; Aakash Shah; Marc I. Lorber; Alison Grazioli; Kapil Saharia; Susie N. Hong; Susan Joseph; David Ayares; Muhammad M. Mohiuddin
Published: Jun 22, 2022
Journal or venue: New England Journal of Medicine
DOI: 10.1056/nejmoa2201422
Paper type: journal article
Source: Openalex

DOI OpenAlex