Engraftment of human iPS cells and allogeneic porcine cells into pigs with inactivated RAG2 and accompanying severe combined immunodeficiency
| Autor: | Craig L. Franklin, Chankyu Park, Eric M. Walters, Deug-Nam Kwon, Alana N. Brown, Melissa Samuel, Kiho Lee, Jae-Hwan Kim, Yun-Jung Choi, Jin-Hoi Kim, Aaron C. Ericsson, Toshihiko Ezashi, Clifton N. Murphy, Dae Young Kim, Kwang-Wook Park, Randall S. Prather, R. Michael Roberts |
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| Jazyk: | angličtina |
| Rok vydání: | 2014 |
| Předmět: |
Genotype
Somatic cell Swine Xenotransplantation medicine.medical_treatment Induced Pluripotent Stem Cells Molecular Sequence Data Transplantation Heterologous Spleen Thymus Gland Biology Umbilical Cord RAG2 medicine Animals Humans Regeneration Induced pluripotent stem cell Alleles Severe combined immunodeficiency Multidisciplinary Base Sequence Nuclear Proteins Biological Sciences Fibroblasts medicine.disease Transplantation DNA-Binding Proteins medicine.anatomical_structure Phenotype Immunology Mutation Swine Miniature Severe Combined Immunodeficiency Stem cell |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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