title: Derivation of Canine Induced Pluripotent Stem Cells.
abstract: Dogs and humans have many inherited genetic diseases in common and conditions that are increasingly prevalent in humans also occur naturally in dogs. The use of dogs for the experimental and clinical testing of stem cell and regenerative medicine products would benefit canine health and welfare and provide relevant animal models for the translation of therapies to the human field. Induced pluripotent stem cells (iPSCs) have the capacity to turn into all cells of the body and therefore have the potential to provide cells for therapeutic use and for disease modelling. The objective of this study was to derive and characterize iPSCs from karyotypically abnormal adult canine cells. Aneuploid adipose-derived mesenchymal stromal cells (AdMSCs) from an adult female Weimeraner were re-programmed into iPSCs via overexpression of four human pluripotency factors (Oct 4, Sox2, Klf4 and c-myc) using retroviral vectors. The iPSCs showed similarity to human ESCs with regard to morphology, pluripotency marker expression and the ability to differentiate into derivatives of all three germ layers in vitro (endoderm, ectoderm and mesoderm). The iPSCs also demonstrated silencing of the viral transgenes and re-activation of the silent X chromosome, suggesting full reprogramming had occurred. The levels of aneuploidy observed in the AdMSCs were maintained in the iPSCs. This finding demonstrates the potential for generating canine induced pluripotent stem cells for use as disease models in addition to regenerative medicine and pharmaceutical testing.
authors.affiliation: Animal Health Trust, Kentford, Newmarket, Suffolk, UK.
authors.forename: Aeg
authors.initials: A
authors.lastname: Baird
authors.affiliation: Animal Health Trust, Kentford, Newmarket, Suffolk, UK.
authors.forename: T
authors.initials: T
authors.lastname: Barsby
authors.affiliation: Animal Health Trust, Kentford, Newmarket, Suffolk, UK.
authors.forename: D J
authors.initials: DJ
authors.lastname: Guest
mesh_terms: D000273:Adipose Tissue / Q000166:cytology; D000818:Animals; D015415:Biomarkers / Q000032:analysis; D002454:Cell Differentiation / Q000502:physiology; D065150:Cellular Reprogramming; D004285:Dogs; D005260:Female; D015870:Gene Expression; D005822:Genetic Vectors; D006801:Humans; D007150:Immunohistochemistry; D057026:Induced Pluripotent Stem Cells / Q000166:cytology / Q000502:physiology*; D000090062:Kruppel-Like Factor 4; D051741:Kruppel-Like Transcription Factors / Q000235:genetics; D059630:Mesenchymal Stem Cells / Q000378:metabolism; D023421:Models, Animal; D050814:Octamer Transcription Factor-3 / Q000235:genetics; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics; D055748:SOXB1 Transcription Factors / Q000235:genetics; D014162:Transfection / Q000662:veterinary
chemical_list: D015415:Biomarkers; C000715467:KLF4 protein, human; D000090062:Kruppel-Like Factor 4; D051741:Kruppel-Like Transcription Factors; C489427:MYC protein, human; D050814:Octamer Transcription Factor-3; C494173:POU5F1 protein, human; D016271:Proto-Oncogene Proteins c-myc; C527782:SOX2 protein, human; D055748:SOXB1 Transcription Factors