title: Derivation of mesenchymal stromal cells from canine induced pluripotent stem cells by inhibition of the TGFβ/activin signaling pathway.
abstract: In this study we have generated canine mesenchymal stromal cells (MSCs), also known as mesenchymal stem cells, from canine induced pluripotent stem cells (ciPSCs) by small-molecule inhibition of the transforming growth factor beta (TGFβ)/activin signaling pathway. These ciPSC-derived MSCs (ciPSC-MSCs) express the MSC markers CD73, CD90, CD105, STRO1, cPDGFRβ and cKDR, in addition to the pluripotency factors OCT4, NANOG and REX1. ciPSC-MSCs lack immunostaining for H3K27me3, suggesting that they possess two active X chromosomes. ciPSC-MSCs are highly proliferative and undergo robust differentiation along the osteo-, chondro- and adipogenic pathways, but do not form teratoma-like tissues in vitro. Of further significance for the translational potential of ciPSC-MSCs, we show that these cells can be encapsulated and maintained within injectable hydrogel matrices that, when functionalized with bound pentosan polysulfate, dramatically enhance chondrogenesis and inhibit osteogenesis. The ability to efficiently derive large numbers of highly proliferative canine MSCs from ciPSCs that can be incorporated into injectable, functionalized hydrogels that enhance their differentiation along a desired lineage constitutes an important milestone towards developing an effective MSC-based therapy for osteoarthritis in dogs, but equally provides a model system for assessing the efficacy and safety of analogous approaches for treating human degenerative joint diseases.
authors: 1 School of Veterinary Science, University of Queensland , Gatton, Queensland, Australia .
authors: Deanne J
authors: DJ
authors: Whitworth
authors: Jessica E
authors: JE
authors: Frith
authors: Thomas J R
authors: TJ
authors: Frith
authors: Dmitry A
authors: DA
authors: Ovchinnikov
authors: Justin J
authors: JJ
authors: Cooper-White
authors: Ernst J
authors: EJ
authors: Wolvetang
mesh_terms: D028341:Activins / Q000378:metabolism*; D000818:Animals; D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism; D002478:Cells, Cultured; D054377:Chemokine CXCL12 / Q000235:genetics / Q000378:metabolism; D020219:Chondrogenesis; D004285:Dogs; D020662:Guanine Nucleotide Exchange Factors / Q000235:genetics / Q000378:metabolism; D006657:Histones / Q000235:genetics / Q000378:metabolism; D057026:Induced Pluripotent Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D050814:Octamer Transcription Factor-3 / Q000235:genetics / Q000378:metabolism; D010012:Osteogenesis; D010426:Pentosan Sulfuric Polyester / Q000494:pharmacology; D020797:Receptor, Platelet-Derived Growth Factor beta / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D016212:Transforming Growth Factor beta / Q000378:metabolism*; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000235:genetics / Q000378:metabolism
chemical_list: D015703:Antigens, CD; D054377:Chemokine CXCL12; D020662:Guanine Nucleotide Exchange Factors; D006657:Histones; D050814:Octamer Transcription Factor-3; D016212:Transforming Growth Factor beta; D028341:Activins; D010426:Pentosan Sulfuric Polyester; D020797:Receptor, Platelet-Derived Growth Factor beta; D040301:Vascular Endothelial Growth Factor Receptor-2