Genetically Modified Porcine-to-Human Cardiac Xenotransplantation

Overview

Journal N Engl J Med

Specialty General Medicine

Date 2022 Jun 22

PMID 35731912

Authors

Bartley P Griffith

Corbin E Goerlich

Avneesh K Singh

Martine Rothblatt

Christine L Lau

Aakash Shah

Marc Lorber

Alison Grazioli

Kapil K Saharia

Susie N Hong

Susan M Joseph

David Ayares

Muhammad M Mohiuddin

Affiliations

Soon will be listed here.

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Sudden diastolic thickening and failure of the xenograft occurred on day 49 after transplantation, and life support was withdrawn on day 60.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.).

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