Research opportunities and ethical considerations for heart and lung xenotransplantation research: A report from the National Heart, Lung, and Blood Institute workshop

Kiran K Khush; James L Bernat; Richard N Pierson 3rd; Henry J Silverman; Brendan Parent; Alexandra K Glazier; Andrew B Adams; Jay A Fishman; Michael Gusmano; Wayne J Hawthorne; Mary E Homan; Daniel J Hurst; Stephen Latham; Chung-Gyu Park; Karen J Maschke; Muhammad M Mohiuddin; Robert A Montgomery; Jonah Odim; Rebecca D Pentz; Bruno Reichart; Julian Savulescu; Paul Root Wolpe; Renee P Wong; Kathleen N Fenton

doi:10.1016/j.ajt.2024.03.015

Research opportunities and ethical considerations for heart and lung xenotransplantation research: A report from the National Heart, Lung, and Blood Institute workshop

Am J Transplant. 2024 Jun;24(6):918-927. doi: 10.1016/j.ajt.2024.03.015. Epub 2024 Mar 19.

Authors

Kiran K Khush¹, James L Bernat², Richard N Pierson 3rd³, Henry J Silverman⁴, Brendan Parent⁵, Alexandra K Glazier⁶, Andrew B Adams⁷, Jay A Fishman⁸, Michael Gusmano⁹, Wayne J Hawthorne¹⁰, Mary E Homan¹¹, Daniel J Hurst¹², Stephen Latham¹³, Chung-Gyu Park¹⁴, Karen J Maschke¹⁵, Muhammad M Mohiuddin¹⁶, Robert A Montgomery¹⁷, Jonah Odim¹⁸, Rebecca D Pentz¹⁹, Bruno Reichart²⁰, Julian Savulescu²¹, Paul Root Wolpe²², Renee P Wong²³, Kathleen N Fenton²⁴

Affiliations

¹ Division of Cardiovascular Medicine, Department of Medicine, Stanford University School of Medicine, Stanford, California, USA. Electronic address: kiran@stanford.edu.
² Department of Neurology, Dartmouth Geisel School of Medicine, Hanover, New Hampshire, USA.
³ Department of Surgery and Center for Transplantation Sciences, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA.
⁴ Department of Medicine, University of Maryland School of Medicine, Baltimore, Maryland, USA.
⁵ Department of Population Health, New York University Grossman School of Medicine, New York, New York, USA.
⁶ New England Donor Services, Waltham, Massachusetts, USA; School of Public Health, Brown University, Providence, Rhode Island, USA.
⁷ Department of Surgery, University of Minnesota, Minneapolis, Minnesota, USA.
⁸ Transplant Infectious Disease and MGH Transplant Center, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA.
⁹ College of Health, Lehigh University, Bethlehem, Pennsylvania, USA.
¹⁰ Department of Surgery, Westmead Hospital, University of Sydney, Westmead, New South Wales, Australia.
¹¹ Department of Theology and Ethics, CommonSpirit Health, Chicago, Illinois, USA.
¹² Department of Family Medicine, Rowan University School of Osteopathic Medicine, Stratford, New Jersey, USA.
¹³ Interdisciplinary Center for Bioethics, Yale University, New Haven, Connecticut, USA.
¹⁴ Department of Microbiology and Immunology, Seoul National University College of Medicine, Seoul, South Korea.
¹⁵ The Hastings Center, Garrison, New York, USA.
¹⁶ Department of Surgery, University of Maryland School of Medicine, Baltimore, Maryland, USA.
¹⁷ NYU Langone Transplant Institute, NYU Langone Health, New York, New York, USA.
¹⁸ Transplantation Branch, Division of Allergy, Immunology, and Transplantation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
¹⁹ Winship Cancer Institute, Emory University School of Medicine, Atlanta, Georgia, USA.
²⁰ Department of Cardiac Surgery, Ludwig-Maximillian University, Munich, Germany.
²¹ Centre for Biomedical Ethics, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
²² Center for Ethics and Department of Medicine, Emory University, Atlanta, Georgia, USA.
²³ Heart Failure and Arrhythmias Branch, Division of Cardiovascular Sciences, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland, USA.
²⁴ Advanced Technologies and Surgery Branch, Division of Cardiovascular Sciences, National Heart, Lung, and Blood Institute, and Department of Bioethics, Clinical Center, National Institutes of Health, Bethesda, Maryland, USA.

PMID: 38514013
PMCID: PMC11144553 (available on 2025-06-01)
DOI: 10.1016/j.ajt.2024.03.015

Abstract

Xenotransplantation offers the potential to meet the critical need for heart and lung transplantation presently constrained by the current human donor organ supply. Much was learned over the past decades regarding gene editing to prevent the immune activation and inflammation that cause early organ injury, and strategies for maintenance of immunosuppression to promote longer-term xenograft survival. However, many scientific questions remain regarding further requirements for genetic modification of donor organs, appropriate contexts for xenotransplantation research (including nonhuman primates, recently deceased humans, and living human recipients), and risk of xenozoonotic disease transmission. Related ethical questions include the appropriate selection of clinical trial participants, challenges with obtaining informed consent, animal rights and welfare considerations, and cost. Research involving recently deceased humans has also emerged as a potentially novel way to understand how xeno-organs will impact the human body. Clinical xenotransplantation and research involving decedents also raise ethical questions and will require consensus regarding regulatory oversight and protocol review. These considerations and the related opportunities for xenotransplantation research were discussed in a workshop sponsored by the National Heart, Lung, and Blood Institute, and are summarized in this meeting report.

Keywords: donors; ethics; research; xenotransplantation.

MeSH terms

Animals
Biomedical Research / ethics
Heart Transplantation* / ethics
Humans
Lung Transplantation* / ethics
National Heart, Lung, and Blood Institute (U.S.)
Tissue Donors / ethics
Tissue Donors / supply & distribution
Transplantation, Heterologous* / ethics
United States

Abstract

MeSH terms

Grants and funding