title: Induced pluripotent stem cell lines derived from equine fibroblasts.
abstract: The domesticated horse represents substantial value for the related sports and recreational fields, and holds enormous potential as a model for a range of medical conditions commonly found in humans. Most notable of these are injuries to muscles, tendons, ligaments and joints. Induced pluripotent stem (iPS) cells have sparked tremendous hopes for future regenerative therapies of conditions that today are not possible to cure. Equine iPS (EiPS) cells, in addition to bringing promises to the veterinary field, open up the opportunity to utilize horses for the validation of stem cell based therapies before moving into the human clinical setting. In this study, we report the generation of iPS cells from equine fibroblasts using a piggyBac (PB) transposon-based method to deliver transgenes containing the reprogramming factors Oct4, Sox2, Klf4 and c-Myc, expressed in a temporally regulated fashion. The established iPS cell lines express hallmark pluripotency markers, display a stable karyotype even during long-term culture, and readily form complex teratomas containing all three embryonic germ layer derived tissues upon in vivo grafting into immunocompromised mice. Our EiPS cell lines hold the promise to enable the development of a whole new range of stem cell-based regenerative therapies in veterinary medicine, as well as aid the development of preclinical models for human applications. EiPS cell could also potentially be used to revive recently extinct or currently threatened equine species.
authors.affiliation: Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, ON, Canada.
authors.forename: Kristina
authors.initials: K
authors.lastname: Nagy
authors.forename: Hoon-Ki
authors.initials: HK
authors.lastname: Sung
authors.forename: Puzheng
authors.initials: P
authors.lastname: Zhang
authors.forename: Simon
authors.initials: S
authors.lastname: Laflamme
authors.forename: Patrick
authors.initials: P
authors.lastname: Vincent
authors.forename: Siamak
authors.initials: S
authors.lastname: Agha-Mohammadi
authors.forename: Knut
authors.initials: K
authors.lastname: Woltjen
authors.forename: Claudio
authors.initials: C
authors.lastname: Monetti
authors.forename: Iacovos Prodromos
authors.initials: IP
authors.lastname: Michael
authors.forename: Lawrence Charles
authors.initials: LC
authors.lastname: Smith
authors.forename: Andras
authors.initials: A
authors.lastname: Nagy
mesh_terms: D000818:Animals; D018929:Cell Culture Techniques; D002460:Cell Line; D064987:Cell- and Tissue-Based Therapy / Q000379:methods; D002478:Cells, Cultured; D065150:Cellular Reprogramming; D005347:Fibroblasts / Q000166:cytology* / Q000502:physiology; D006736:Horses; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000166:cytology* / Q000502:physiology; D000090062:Kruppel-Like Factor 4; D051379:Mice; D012038:Regeneration; D019076:Transgenes