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The Case for Cardiac Xenotransplantation in Neonates: Is Now the Time to Reconsider Xenotransplantation for Hypoplastic Left Heart Syndrome?

  • David Cleveland
  • C. Adam Banks
  • Hidetaka Hara
  • Waldemar F. Carlo
  • David C. Mauchley
  • David K. C. Cooper
Original Article

Abstract

Neonatal cardiac transplantation for hypoplastic left heart syndrome (HLHS) is associated with excellent long-term survival compared to older recipients. However, heart transplantation for neonates is greatly limited by the critical shortage of donor hearts, and by the associated mortality of the long pre-transplant waiting period. This led to the development of staged surgical palliation as the first-line surgical therapy for HLHS. Recent advances in genetic engineering and xenotransplantation have provided the potential to replicate the excellent results of neonatal cardiac allotransplantation while eliminating wait-list-associated mortality through genetically modified pig-to-human neonatal cardiac xenotransplantation. The elimination of the major pig antigens in addition to the immature B-cell response in neonates allows for the potential to induce B-cell tolerance. Additionally, the relatively mature neonatal T-cell response could be reduced by thymectomy at the time of operation combined with donor-specific pig thymus transplantation to “reprogram” the host’s T-cells to recognize the xenograft as host tissue. In light of the recent significantly increased graft survival of genetically-engineered pig-to-baboon cardiac xenotransplantation, we propose that now is the time to consider devoting research to advance the potential clinical application of cardiac xenotransplantation as a treatment option for patients with HLHS. Employing cardiac xenotransplantation could revolutionize therapy for complex congenital heart defects and open a new chapter in the field of pediatric cardiac transplantation.

Keywords

Congenital heart disease Immunological tolerance Pig Genetically-engineered Staged surgical palliation Xenotransplantation 

Abbreviations

GEP

Genetically engineered pig

GTKO

α1,3-Galactosyltansferase gene-knockout

HLHS

Hypoplastic left heart syndrome

NHP

Nonhuman primate

Notes

Acknowledgements

We thank Leonard Bailey, MD, and James Fitts from the Department of Pediatric Cardiovascular Surgery, Loma Linda University International Heart Institute, Loma Linda, CA, for generously providing their current data to us. C.A.B. thanks the UAB School of Medicine and the Department of Surgery for funding that enabled him to participate in the preparation of this manuscript. Work on xenotransplantation at the University of Alabama at Birmingham is supported in part by NIH NIAID U19 Grant AI090959.

Compliance with Ethical Standards

Conflict of interest

The authors declare that they have no conflict of interest.

Research Involving Human Participants and/or Animals

This article is a review of the literature and does not contain any studies with human participants or animals performed by any of the authors.

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • David Cleveland
    • 1
  • C. Adam Banks
    • 1
  • Hidetaka Hara
    • 2
  • Waldemar F. Carlo
    • 3
  • David C. Mauchley
    • 1
  • David K. C. Cooper
    • 2
  1. 1.Division of Pediatric Cardiovascular SurgeryUniversity of Alabama at BirminghamBirminghamUSA
  2. 2.Xenotransplantation Program, Department of SurgeryUniversity of Alabama at BirminghamBirminghamUSA
  3. 3.Section of Pediatric CardiologyUniversity of Alabama at BirminghamBirminghamUSA

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