ArticleXenotransplantation2021
Mixed xenogeneic porcine chimerism tolerizes human anti-pig natural antibody-producing cells in a humanized mouse model.
Article in Xenotransplantation, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
What it found
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The trial behind it
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Who cites it
7 citing papers in PubMed, 9 citations in OpenAlex.
- Transgenic expression of human CD47 on pig cells provides only partial protection against human macrophage-mediated destruction in human immune system mice.American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons · 2026Article
- T Cell Development and Responses in Human Immune System Mice.Annual review of immunology · 2025Review
- OMIP-108: 22-color flow cytometry panel for detection and monitoring of chimerism and immune reconstitution in porcine-to-baboon models of operational xenotransplant tolerance studies.Cytometry. Part A : the journal of the International Society for Analytical Cytology · 2024Article
- Enhancing Kidney Transplantation and the Role of Xenografts: Report of a Scientific Workshop Sponsored by the National Kidney Foundation.American journal of kidney diseases : the official journal of the National Kidney Foundation · 2024Review
- Progress in xenotransplantation: overcoming immune barriers.Nature reviews. Nephrology · 2022Review
- Developing pig-to-human organ transplants.Science (New York, N.Y.) · 2022Article
- Chimerism-Based Tolerance to Kidney Allografts in Humans: Novel Insights and Future Perspectives.Frontiers in immunology · 2021Review
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 2 countries.
Funding
Abstract
backgroundA major obstacle to the success of organ transplantation from pigs to humans, necessitated by the shortage of human organs, is robust humoral immune rejection by pig-reactive human antibodies. Mixed xenogeneic hematopoietic chimerism induces xenoreactive B cell tolerance in rodents, but whether mixed pig/human chimerism could induce tolerance of human B cells to pig xenoantigens is unknown.
methodsWe investigated this question using a humanized mouse model in which durable mixed (pig-human) xenogeneic chimerism can be established.
resultsHuman natural anti-pig cytotoxic antibodies, predominantly IgM, are detectable in non-chimeric humanized mouse serum, and pig-reactive antibodies were reduced in mixed chimeric versus non-chimeric humanized mice. This difference required persistent mixed chimerism and was not due to the adsorption of antibodies on pig cells in vivo. Furthermore, human B cells from spleens of mixed chimeric mice produced lower levels of anti-pig antibodies when stimulated in vitro compared with those from non-chimeric mice.
conclusionsOur findings demonstrate that mixed chimerism reduces human natural antibodies to pig xenoantigens, providing the first in vivo evidence of human B cell tolerance induction by mixed xenogeneic chimerism and supporting further evaluation of this approach for inducing human B cell tolerance to xenografts.
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