title: Monomeric, porous type II collagen scaffolds promote chondrogenic differentiation of human bone marrow mesenchymal stem cells in vitro.
abstract: Osteoarthritis (OA) is a common cause of pain and disability and is often associated with the degeneration of articular cartilage. Lesions to the articular surface, which are thought to progress to OA, have the potential to be repaired using tissue engineering strategies; however, it remains challenging to instruct cell differentiation within a scaffold to produce tissue with appropriate structural, chemical and mechanical properties. We aimed to address this by driving progenitor cells to adopt a chondrogenic phenotype through the tailoring of scaffold composition and physical properties. Monomeric type-I and type-II collagen scaffolds, which avoid potential immunogenicity associated with fibrillar collagens, were fabricated with and without chondroitin sulfate (CS) and their ability to stimulate the chondrogenic differentiation of human bone marrow-derived mesenchymal stem cells was assessed. Immunohistochemical analyses showed that cells produced abundant collagen type-II on type-II scaffolds and collagen type-I on type-I scaffolds. Gene expression analyses indicated that the addition of CS - which was released from scaffolds quickly - significantly upregulated expression of type II collagen, compared to type-I and pure type-II scaffolds. We conclude that collagen type-II and CS can be used to promote a more chondrogenic phenotype in the absence of growth factors, potentially providing an eventual therapy to prevent OA.
authors.affiliation: Department of Materials, University of Oxford, Oxford OX1 3PH, UK.|Craniofacial Development and Stem Cell Biology, King's College London, London SE1 9RT, UK.
authors.forename: M
authors.initials: M
authors.lastname: Tamaddon
authors.affiliation: Craniofacial Development and Stem Cell Biology, King's College London, London SE1 9RT, UK.
authors.forename: M
authors.initials: M
authors.lastname: Burrows
authors.affiliation: Craniofacial Development and Stem Cell Biology, King's College London, London SE1 9RT, UK.
authors.forename: S A
authors.initials: SA
authors.lastname: Ferreira
authors.affiliation: Division of Cancer Studies, Rayne Institute, King's College London, London SE5 9NU, UK.
authors.forename: F
authors.initials: F
authors.lastname: Dazzi
authors.affiliation: Centre for Haematology, Department of Medicine, Imperial College London, London W12 0NN, UK.|John Goldman Centre for Cellular Therapy, Imperial College Healthcare NHS Trust, London W12 0HS, UK.
authors.forename: J F
authors.initials: JF
authors.lastname: Apperley
authors.affiliation: John Goldman Centre for Cellular Therapy, Imperial College Healthcare NHS Trust, London W12 0HS, UK.
authors.forename: A
authors.initials: A
authors.lastname: Bradshaw
authors.affiliation: Research Service, Memphis VA Medical Center, Departments of Medicine and Microbiology, Immunology and Biochemistry, University of Tennessee Health Science Center, Memphis, TN 38104, USA.
authors.forename: D D
authors.initials: DD
authors.lastname: Brand
authors.affiliation: Department of Materials, University of Oxford, Oxford OX1 3PH, UK.
authors.forename: J
authors.initials: J
authors.lastname: Czernuszka
authors.affiliation: Craniofacial Development and Stem Cell Biology, King's College London, London SE1 9RT, UK.
authors.forename: E
authors.initials: E
authors.lastname: Gentleman
mesh_terms: D015415:Biomarkers; D018929:Cell Culture Techniques; D002454:Cell Differentiation / Q000235:genetics; D002470:Cell Survival; D002478:Cells, Cultured; D020219:Chondrogenesis; D024042:Collagen Type I / Q000378:metabolism; D024043:Collagen Type II / Q000737:chemistry / Q000378:metabolism*; D005109:Extracellular Matrix; D006801:Humans; D055595:Mechanical Phenomena; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000378:metabolism; D023822:Tissue Engineering; D054457:Tissue Scaffolds / Q000737:chemistry
chemical_list: D015415:Biomarkers; D024042:Collagen Type I; D024043:Collagen Type II