title: Generation, Characterization, and Multilineage Potency of Mesenchymal-Like Progenitors Derived from Equine Induced Pluripotent Stem Cells.
abstract: Multipotent mesenchymal stromal cells (MSCs) are more and more frequently used to treat orthopedic injuries in horses. However, these cells are limited in their expandability and differentiation capacity. Recently, the first equine-induced pluripotent stem cell (iPSC) lines were reported by us [ 1 ]. In vitro differentiation of iPSCs into MSC-like cells is an attractive alternative to using MSCs derived from other sources, as a much larger quantity of patient-specific cells with broad differentiation potential could be generated. However, the differentiation capacity of iPSCs to MSCs and the potential for use in tissue engineering have yet to be explored. In this study, equine iPSCs were induced to differentiate into an MSC-like population. Upon induction, the iPSCs changed morphology toward spindle-shaped cells similar to MSCs. The ensuing iPSC-MSCs exhibited downregulation of pluripotency-associated genes and an upregulation of MSC-associated genes. In addition, the cells expressed the same surface markers as MSCs derived from equine umbilical cord blood. We then assessed the multilineage differentiation potential of iPSC-MSCs. Although chondrogenesis was not achieved after induction with transforming growth factor-beta 3 (TGFβ3) and/or bone morphogenic protein 4 (BMP-4) in 3D pellet culture, mineralization characteristic of osteogenesis and lipid droplet accumulation characteristic of adipogenesis were observed after chemical induction. We demonstrate a protocol for the derivation of MSC-like progenitor populations from equine iPS cells.
authors.affiliation: 1 Department of Biomedical Sciences, University of Guelph , Guelph, Ontario, Canada .
authors.forename: Sarah I
authors.initials: SI
authors.lastname: Lepage
authors.affiliation: 2 Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital , Toronto, Ontario, Canada .
authors.forename: Kristina
authors.initials: K
authors.lastname: Nagy
authors.affiliation: 2 Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital , Toronto, Ontario, Canada .
authors.forename: Hoon-Ki
authors.initials: HK
authors.lastname: Sung
authors.affiliation: 3 Institute of Biomaterials and Biomedical Engineering, University of Toronto , Toronto, Ontario, Canada .|4 Pathology and Experimental Medicine, Mount Sinai Hospital , Toronto, Ontario, Canada .
authors.forename: Rita A
authors.initials: RA
authors.lastname: Kandel
authors.affiliation: 2 Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital , Toronto, Ontario, Canada .|5 Department of Obstetrics and Gynecology and Institute of Medical Science, University of Toronto , Toronto, Ontario, Canada .
authors.forename: Andras
authors.initials: A
authors.lastname: Nagy
authors.affiliation: 1 Department of Biomedical Sciences, University of Guelph , Guelph, Ontario, Canada .|6 Department of Clinical Studies, Orthopedic Research Lab, Aarhus University , Aarhus, Denmark .
authors.forename: Thomas G
authors.initials: TG
authors.lastname: Koch
mesh_terms: D050156:Adipogenesis / Q000502:physiology; D000818:Animals; D018929:Cell Culture Techniques / Q000662:veterinary; D002454:Cell Differentiation; D002469:Cell Separation; D002478:Cells, Cultured; D065150:Cellular Reprogramming; D020219:Chondrogenesis / Q000502:physiology; D006736:Horses; D057026:Induced Pluripotent Stem Cells / Q000166:cytology / Q000502:physiology*; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000502:physiology*; D051379:Mice; D010012:Osteogenesis / Q000502:physiology; D023822:Tissue Engineering / Q000662:veterinary