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Novel Engraftment and T Cell Differentiation of Human Hematopoietic Cells in ART-/-IL2RG-/Y SCID Pigs.
Boettcher, Adeline N; Li, Yunsheng; Ahrens, Amanda P; Kiupel, Matti; Byrne, Kristen A; Loving, Crystal L; Cino-Ozuna, A Giselle; Wiarda, Jayne E; Adur, Malavika; Schultz, Blythe; Swanson, Jack J; Snella, Elizabeth M; Ho, Chak-Sum Sam; Charley, Sara E; Kiefer, Zoe E; Cunnick, Joan E; Putz, Ellie J; Dell'Anna, Giuseppe; Jens, Jackie; Sathe, Swanand; Goldman, Frederick; Westin, Erik R; Dekkers, Jack C M; Ross, Jason W; Tuggle, Christopher K.
Afiliación
  • Boettcher AN; Department of Animal Science, Iowa State University, Ames, IA, United States.
  • Li Y; Department of Animal Science, Iowa State University, Ames, IA, United States.
  • Ahrens AP; Laboratory Animal Resources, Iowa State University, Ames, IA, United States.
  • Kiupel M; Department of Pathobiology and Diagnostic Investigation, College of Veterinary Medicine, Michigan State University, East Lansing, MI, United States.
  • Byrne KA; Food Safety and Enteric Pathogen Unit, National Animal Disease Center, US Department of Agriculture, Agricultural Research Service, Ames, IA, United States.
  • Loving CL; Food Safety and Enteric Pathogen Unit, National Animal Disease Center, US Department of Agriculture, Agricultural Research Service, Ames, IA, United States.
  • Cino-Ozuna AG; Veterinary Diagnostic Laboratory, Kansas State University, Manhattan, KS, United States.
  • Wiarda JE; Food Safety and Enteric Pathogen Unit, National Animal Disease Center, US Department of Agriculture, Agricultural Research Service, Ames, IA, United States.
  • Adur M; Immunobiology Graduate Program, College of Veterinary Medicine, Iowa State University, Ames, IA, United States.
  • Schultz B; Oak Ridge Institute for Science and Education, Agricultural Research Service Participation Program, Oak Ridge, TN, United States.
  • Swanson JJ; Department of Animal Science, Iowa State University, Ames, IA, United States.
  • Snella EM; Department of Animal Science, Iowa State University, Ames, IA, United States.
  • Ho CS; McFarland Clinic, Ames, IA, United States.
  • Charley SE; Department of Animal Science, Iowa State University, Ames, IA, United States.
  • Kiefer ZE; Gift of Hope Organ and Tissue Donor Network, Itasca, IL, United States.
  • Cunnick JE; Department of Animal Science, Iowa State University, Ames, IA, United States.
  • Putz EJ; Department of Animal Science, Iowa State University, Ames, IA, United States.
  • Dell'Anna G; Department of Animal Science, Iowa State University, Ames, IA, United States.
  • Jens J; Department of Animal Science, Iowa State University, Ames, IA, United States.
  • Sathe S; Laboratory Animal Resources, Iowa State University, Ames, IA, United States.
  • Goldman F; Department of Animal Science, Iowa State University, Ames, IA, United States.
  • Westin ER; Veterinary Clinical Sciences, Iowa State University, Ames, IA, United States.
  • Dekkers JCM; Department of Pediatrics, University of Alabama, Birmingham, AL, United States.
  • Ross JW; Department of Pediatrics, University of Alabama, Birmingham, AL, United States.
  • Tuggle CK; Department of Animal Science, Iowa State University, Ames, IA, United States.
Front Immunol ; 11: 100, 2020.
Article en En | MEDLINE | ID: mdl-32117254
ABSTRACT
Pigs with severe combined immunodeficiency (SCID) are an emerging biomedical animal model. Swine are anatomically and physiologically more similar to humans than mice, making them an invaluable tool for preclinical regenerative medicine and cancer research. One essential step in further developing this model is the immunological humanization of SCID pigs. In this work we have generated T- B- NK- SCID pigs through site directed CRISPR/Cas9 mutagenesis of IL2RG within a naturally occurring DCLRE1C (ARTEMIS)-/- genetic background. We confirmed ART-/-IL2RG-/Y pigs lacked T, B, and NK cells in both peripheral blood and lymphoid tissues. Additionally, we successfully performed a bone marrow transplant on one ART-/-IL2RG-/Y male SCID pig with bone marrow from a complete swine leukocyte antigen (SLA) matched donor without conditioning to reconstitute porcine T and NK cells. Next, we performed in utero injections of cultured human CD34+ selected cord blood cells into the fetal ART-/-IL2RG-/Y SCID pigs. At birth, human CD45+ CD3ε+ cells were detected in cord and peripheral blood of in utero injected SCID piglets. Human leukocytes were also detected within the bone marrow, spleen, liver, thymus, and mesenteric lymph nodes of these animals. Taken together, we describe critical steps forwards the development of an immunologically humanized SCID pig model.
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Texto completo: 1 Base de datos: MEDLINE Asunto principal: Trasplante de Médula Ósea / Inmunodeficiencia Combinada Grave / Subunidad gamma Común de Receptores de Interleucina Idioma: En Revista: Front Immunol Año: 2020 Tipo del documento: Article
Texto completo
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Base de datos: MEDLINE Asunto principal: Trasplante de Médula Ósea / Inmunodeficiencia Combinada Grave / Subunidad gamma Común de Receptores de Interleucina Idioma: En Revista: Front Immunol Año: 2020 Tipo del documento: Article