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Related Experiment Video

Updated: Jun 3, 2025

A Porcine Heterotopic Heart Transplantation Protocol for Delivery of Therapeutics to a Cardiac Allograft
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A Porcine Heterotopic Heart Transplantation Protocol for Delivery of Therapeutics to a Cardiac Allograft

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Genetically engineered pig heart transplantation in non-human primates.

Avneesh K Singh1, Corbin E Goerlich1,2, Tianshu Zhang1

  • 1Department of Surgery, The University of Maryland School of Medicine, Baltimore, MD, USA.

Communications Medicine
|January 8, 2025
PubMed
Summary

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Gene-edited pig hearts show promise for xenotransplantation, with 10 gene edits improving survival in non-human primates. These advancements support clinical trials and compassionate use in cardiac xenotransplantation.

Area of Science:

  • Xenotransplantation research
  • Gene editing in animal models
  • Cardiovascular surgery

Background:

  • Advancements in gene-edited donor pigs have reduced early cardiac xenograft rejection and improved survival in non-human primate models.
  • These improvements paved the way for FDA approval of compassionate use cardiac xenotransplantation in two patients.

Purpose of the Study:

  • To evaluate the efficacy of 10 gene-edited (10-GE) pig hearts in baboon recipients.
  • To assess long-term cardiac xenograft survival and function using a novel preservation and immunosuppression strategy.

Main Methods:

  • Transplantation of 10-GE pig hearts into baboons (n=4) using life-supporting orthotopic transplantation.
  • Utilized non-ischemic continuous perfusion preservation (NICP) and a co-stimulation blockade immunosuppression regimen (anti-CD40 mAb).

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  • Expanded upon a previous 7-GE model with three additional gene edits.

    • Main Results:

    • 10-GE cardiac xenografts provided life-supporting function for up to 225 days (mean 128 days) in baboons.
    • Porcine cytomegalovirus (PCMV) presence did not impact xenograft survival in this cohort.
    • Histological findings included adipose deposition, chronic vasculopathy, thrombosis, and acute cellular rejection in some xenografts.

    Conclusions:

    • 10-GE cardiac xenografts demonstrate variable survival in non-human primates, potentially due to unaddressed antigens.
    • Despite variability, 10-GE pig hearts show suitability for clinical cardiac xenotransplantation.
    • These organs have already been used in two human compassionate use cases.