title: Bespoke human hypertrophic chondrocytic cell lines provide the osteoinductive signals required for vascularized bone formation.
abstract: Hypertrophic cartilage provides the morphological and biochemical template for orchestrating bone growth. To produce a bone-inductive material such as hypertrophic cartilage for clinical use, we have conditionally immortalized hypertrophic chondrocytic cells from human femur and expanded them in vitro through more than 145 divisions. The clonal cell lines generated by this process consistently express signals that induce both rat and human marrow cells to differentiate in vitro into osteoblastic cells. Further, implantation of the cell-free extracellular matrix from the immortalized chondrocytic cells causes vascularized bone to form in vivo in bony defects, but not in ectopic sites such as skeletal muscle. This study shows that molecular techniques can be used to generate bespoke human cell lines for bone tissue engineering. It also demonstrates that matrix material generated from human immortalized hypertrophic chondrocytic cells may provide an abundant, efficacious, and safer alternative to bone autograft--the currently preferred material for fracture repair.
authors.affiliation: School of Dentistry, Cardiff University, Cardiff, UK. stringerbm@cardiff.ac.uk
authors.forename: Bradley
authors.initials: B
authors.lastname: Stringer
authors.forename: Rachel
authors.initials: R
authors.lastname: Waddington
authors.forename: Alastair
authors.initials: A
authors.lastname: Sloan
authors.forename: Ian
authors.initials: I
authors.lastname: Phillips
authors.forename: Gary
authors.initials: G
authors.lastname: Telford
authors.forename: David
authors.initials: D
authors.lastname: Hughes
authors.forename: Geoffrey
authors.initials: G
authors.lastname: Craig
authors.forename: Lavinia
authors.initials: L
authors.lastname: Gangemi
authors.forename: Ian
authors.initials: I
authors.lastname: Brook
authors.forename: Christine
authors.initials: C
authors.lastname: Freeman
authors.forename: Xuesong
authors.initials: X
authors.lastname: Cao
authors.forename: Mandeep
authors.initials: M
authors.lastname: Gosal
authors.forename: Simon
authors.initials: S
authors.lastname: Smith
authors.forename: Graham
authors.initials: G
authors.lastname: Russell
authors.forename: George
authors.initials: G
authors.lastname: Foster
mesh_terms: D000818:Animals; D002461:Cell Line, Transformed; D002472:Cell Transformation, Viral / Q000502:physiology; D019902:Chondrocytes / Q000473:pathology / Q000502:physiology*; D002999:Clone Cells; D006801:Humans; D006984:Hypertrophy; D008297:Male; D009389:Neovascularization, Pathologic; D018919:Neovascularization, Physiologic / Q000502:physiology*; D010012:Osteogenesis / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction / Q000502:physiology*