ArticleProceedings of the National Academy of Sciences of the United States of America2014
Engraftment of human iPS cells and allogeneic porcine cells into pigs with inactivated RAG2 and accompanying severe combined immunodeficiency.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 83 papers.
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Who cites it
83 citing papers in PubMed, 115 citations in OpenAlex.
- Recent advances in the construction of humanized animal models and applications in translational medicine.Animal models and experimental medicine · 2026Review
- JAK3-deficient mini-pigs exhibit impaired lymphoid organogenesis, intestinal structure, and leukocyte/cytokine production.Journal of advanced research · 2026Article
- Evolutionary insights and structural characterization guide the development of RAG1/RAG2-deficient swine models for immunological research.Frontiers in immunology · 2026Article
- Long-term engraftment of human stem and progenitor cells for large-scale production of functional immune cells in engineered pigs.Nature biomedical engineering · 2025Article
- A bibliometric mapping of advancements and trends in genome editing in pigs.Tropical animal health and production · 2025Review
- Gene Editing for Enhanced Swine Production: Current Advances and Prospects.Animals : an open access journal from MDPI · 2025Review
- Advances and applications of genome-edited animal models for severe combined immunodeficiency.Zoological research · 2025Review
- Fetal bone engraftment reconstitutes the immune system in pigs with severe combined immunodeficiency.Lab animal · 2024Article
- EFFECT OF GENOTYPE AND AGE ON A DEFINED MICROBIOTA IN GNOTOBIOTIC SCID PIGLETS.bioRxiv : the preprint server for biology · 2024Article
- Generation of RAG2 Knockout Immune-Deficient Miniature Pigs.Animals : an open access journal from MDPI · 2024Article
- The Role of Large Animal Models in Cardiac Regeneration Research Using Human Pluripotent Stem Cell-Derived Cardiomyocytes.Current cardiology reports · 2023Review
- The preclinical and clinical progress of cell sheet engineering in regenerative medicine.Stem cell research & therapy · 2023Review
- Inactivation of growth differentiation factor 9 blocks folliculogenesis in pigs†.Biology of reproduction · 2023Article
- Transplantation of human cells into Interleukin-2 receptor gamma gene knockout pigs under several conditions.Regenerative therapy · 2022Article
- Ex vivo expanded human regulatory T cells modify neuroinflammation in a preclinical model of Alzheimer's disease.Acta neuropathologica communications · 2022Article
- In Vivo Modeling of Human Breast Cancer Using Cell Line and Patient-Derived Xenografts.Journal of mammary gland biology and neoplasia · 2022Review
- Advances in pig models of human diseases.Animal models and experimental medicine · 2022Review
- Generation of immunodeficient pig with hereditary tyrosinemia type 1 and their preliminary application for humanized liver.Cell & bioscience · 2022Article
- Swine models for translational oncological research: an evolving landscape and regulatory considerations.Mammalian genome : official journal of the International Mammalian Genome Society · 2022Review
- Limited Expansion of Human Hepatocytes in FAH/Tissue engineering. Part A · 2022Article
23 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
17 authors at 4 institutions in 3 countries.
Funding
Abstract
Pigs with severe combined immunodeficiency (SCID) may provide useful models for regenerative medicine, xenotransplantation, and tumor development and will aid in developing therapies for human SCID patients. Using a reporter-guided transcription activator-like effector nuclease (TALEN) system, we generated targeted modifications of recombination activating gene (RAG) 2 in somatic cells at high efficiency, including some that affected both alleles. Somatic-cell nuclear transfer performed with the mutated cells produced pigs with RAG2 mutations without integrated exogenous DNA. Biallelically modified pigs either lacked a thymus or had one that was underdeveloped. Their splenic white pulp lacked B and T cells. Under a conventional housing environment, the biallelic RAG2 mutants manifested a "failure to thrive" phenotype, with signs of inflammation and apoptosis in the spleen compared with age-matched wild-type animals by the time they were 4 wk of age. Pigs raised in a clean environment were healthier and, following injection of human induced pluripotent stem cells (iPSCs), quickly developed mature teratomas representing all three germ layers. The pigs also tolerated grafts of allogeneic porcine trophoblast stem cells. These SCID pigs should have a variety of uses in transplantation biology.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.