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Cited by 55Xenotransplantation and immune responseAnimal Genetics and ReproductionTransplantation: Methods and Outcomes

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Progress in Xenotransplantation: Immunologic Barriers, Advances in Gene Editing, and Successful Tolerance Induction Strategies in Pig-To-Primate Transplantation

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Eisenson, Daniel L., Hisadome, Yu, Yamada, Kazuhiko·2022·Frontiers in Immunology
DOI 10.3389/fimmu.2022.899657PMC PMC9157571
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Abstract

Organ transplantation is the most effective treatment for end stage organ failure, but there are not enough organs to meet burgeoning demand. One potential solution to this organ shortage is xenotransplantation using pig tissues. Decades of progress in xenotransplantation, accelerated by the development of rapid genome editing tools, particularly the advent of CRISPR-Cas9 gene editing technologies, have enabled remarkable advances in kidney and heart xenotransplantation in pig-to-nonhuman primates. These breakthroughs in large animal preclinical models laid the foundation for three recent pig-to-human transplants by three different groups: two kidney xenografts in brain dead recipients deemed ineligible for transplant, and one heart xenograft in the first clinical grade study of pig-to-human transplantation. However, despite tremendous progress, recent data including the first clinical case suggest that gene-modification alone will not overcome all xenogeneic immunologic barriers, and thus an active and innovative immunologic strategy is required for successful xenotransplantation. This review highlights xenogeneic immunologic barriers, advances in gene editing, and tolerance-inducing strategies in pig-to-human xenotransplantation.

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Figure 1 Vascularized donor thymic graft transplantation. (A) Porcine composite “thymokidney” at 5 weeks after thymic tissue implantation under own renal capsule, and (B) histology of the thymokidney (HE). (C) Co-transplantation of porcine vascularized thymic lobe and kidney graft in a baboon. White arrows indicate thymic grafts.
Figure 1 Vascularized donor thymic graft transplantation. (A) Porcine composite “thymokidney” at 5 weeks after thymic tissue implantation under own renal capsule, and (B) histology of the thymokidney (HE). (C) Co-transplantation of porcine vascularized thymic lobe and kidney graft in a baboon. White arrows indicate thymic grafts.CC BY · PubMed Central

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Metadata

Authors
Eisenson, D. L., Hisadome, Y., & Yamada, K.
Affiliations
  • Johns Hopkins University (US)
  • Columbia University Irving Medical Center (US)
Corresponding author
Yamada, Kazuhiko
ORCID
Venue
Frontiers in Immunology
Publisher
Frontiers Media SA
Published
2022-05-18
Volume
13
Pages
899657-899657
ISSN
1664-3224 (ISSN-L)
DOI
10.3389/fimmu.2022.899657
PMC
PMC9157571
OpenAlex
W4280513190
Cited by
55
References
0
Citations by year
2026: 13 · 2025: 21 · 2024: 10 · 2023: 7 · 2022: 4
FWCI
2.49
Type
journal article
Language
en
Open access
Licence
Locations
  • Frontiers in Immunology (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
Funders
National Institute of Allergy and Infectious Diseases
Topics
  • Health Sciences › Medicine › Surgery › Xenotransplantation and immune response
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Animal Genetics and Reproduction
  • Health Sciences › Medicine › Surgery › Transplantation: Methods and Outcomes
Keywords
xenotransplantation, pig-to-primate xenotransplantation, pig-to-human xenotransplantation, CRISPR/Cas9 genome editing, tolerance induction, xenotransplantation immunology, organ shortage
MeSH terms
Gene Editing, Animals, Humans, Immune Tolerance, Primates, Swine, Transplantation, Heterologous, Transplantation Tolerance

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