title: Formation of cartilage and synovial tissue by human gingival stem cells.
abstract: Human gingival stem cells (HGSCs) can be easily isolated and manipulated in culture to investigate their multipotency. Osteogenic differentiation of bone-marrow-derived mesenchymal stem/stromal cells has been well documented. HGSCs derive from neural crests, however, and their differentiation capacity has not been fully established. The aim of the present report was to investigate whether HGSCs can be induced to differentiate to osteoblasts and chondrocytes. HGSCs were cultured either in a classical monolayer culture or in three-dimensional floating micromass pellet cultures in specific differentiation media. HGSC differentiation to osteogenic and chondrogenic lineages was determined by protein and gene expression analyses, and also by specific staining of cells and tissue pellets. HGSCs cultured in osteogenic differentiation medium showed induction of Runx2, alkaline phosphatase (ALPL), and osterix expression, and subsequently formed mineralized nodules consistent with osteogenic differentiation. Interestingly, HGSC micromass cultures maintained in chondrogenic differentiation medium showed SOX9-dependent differentiation to both chondrocyte and synoviocyte lineages. Chondrocytes at different stages of differentiation were identified by gene expression profiles and by histochemical and immunohistochemical staining. In 3-week-old cultures, peripheral cells in the micromass cultures organized in layers of cuboidal cells with villous structures facing the medium. These cells were strongly positive for cadherin-11, a marker of synoviocytes. In summary, the findings indicate that HGSCs have the capacity to differentiate to osteogenic, chondrogenic, and synoviocyte lineages. Therefore, HGSCs could serve as an alternative source for stem cell therapies in regenerative medicine for patients with cartilage and joint destructions, such as observed in rheumatoid arthritis.
authors.affiliation: 1 INSERM UMR 1138, Laboratory of Oral Molecular Physiopathology, Cordeliers Research Center, Team 5, Paris Diderot, Pierre and Marie Curie, Paris Descartes Universities , Paris, France .
authors.forename: François Côme
authors.initials: FC
authors.lastname: Ferré
authors.forename: Hannu
authors.initials: H
authors.lastname: Larjava
authors.forename: Ludwig-Stanislas
authors.initials: LS
authors.lastname: Loison-Robert
authors.forename: Tsouria
authors.initials: T
authors.lastname: Berbar
authors.forename: Gethin R
authors.initials: GR
authors.lastname: Owen
authors.forename: Ariane
authors.initials: A
authors.lastname: Berdal
authors.forename: Hafida
authors.initials: H
authors.lastname: Chérifi
authors.forename: Bruno
authors.initials: B
authors.lastname: Gogly
authors.forename: Lari
authors.initials: L
authors.lastname: Häkkinen
authors.forename: Benjamin P J
authors.initials: BP
authors.lastname: Fournier
mesh_terms: D000943:Antigens, Differentiation / Q000096:biosynthesis; D002356:Cartilage / Q000166:cytology / Q000378:metabolism*; D002478:Cells, Cultured; D019902:Chondrocytes / Q000166:cytology / Q000378:metabolism*; D005881:Gingiva / Q000166:cytology / Q000378:metabolism*; D006801:Humans; D010006:Osteoblasts / Q000166:cytology / Q000378:metabolism*; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism*; D013583:Synovial Membrane / Q000166:cytology / Q000378:metabolism*
chemical_list: D000943:Antigens, Differentiation