title: Osteoblastic differentiation of Wharton jelly biopsy specimens and their mesenchymal stromal cells after serum-free culture.
abstract: BACKGROUND
  Cleft lip and cleft palate are increasingly being detected by prenatal ultrasound, which raises the opportunity of using the patient's own osteogenicity from umbilical cord mesenchymal cells for bony repair. The authors address the growth of the cells under a fully defined and regulated protocol.
  
  
  METHODS
  Wharton jelly-derived mesenchymal stromal cells were isolated and expanded as a monolayer with defined serum-free medium. Osteoblastic differentiation was tested in the cells and in the entire Wharton jelly biopsy specimens. The serum-free-cultured cells were included in hydroxyapatite granule-fibrin constructs and, without predifferentiation, subcutaneously implanted into immunoincompetent mice.
  
  
  RESULTS
  Isolation and expansion of Wharton jelly-derived mesenchymal stromal cells were consistently successful under serum-free conditions, and the cells expressed standard mesenchymal stromal cell markers. The serum-free-cultivated cells produced a mineralized extracellular matrix under osteogenic differentiation, with a significant increase of osteoblastic lineage gene expression (Hox-A10 and Runx2) and an up-regulation of downstream osteogenic genes (OSX, OCN, ALPL, and BSP2). In vivo, they formed a dense matrix adjacent to the granules after 8 weeks, but no lamellar bone. serum-free-cultivated entire Wharton jelly biopsy specimens produced a mineralized extracellular matrix within the collagen matrix of the Wharton jelly.
  
  
  CONCLUSIONS
  The osteogenic differentiation potential of Wharton jelly-derived mesenchymal stromal cells was maintained under serum-free isolation and expansion techniques. The cells without predifferentiation form a dense collagen matrix but not bone in vivo. Moreover, entire Wharton jelly biopsy specimens showed periosteal-like mineralization under osteogenic differentiation, which offers new options for autologous bone tissue engineering, including cleft palate surgery.
authors.affiliation: Meyzieu and Lyon, France; and Basel, Switzerland From CTI-BIOTECH, Cell Therapy Research Institute; the Department of Biomedicine, University and University Hospital of Basel; Craniomaxillofacial Surgery, University Hospital Basel; Novotec; and the Faculty of Pharmacy, University Claude Bernard Lyon.
authors.forename: Andreas A
authors.initials: AA
authors.lastname: Mueller
authors.forename: Nico
authors.initials: N
authors.lastname: Forraz
authors.forename: Sinan
authors.initials: S
authors.lastname: Gueven
authors.forename: Gianluigi
authors.initials: G
authors.lastname: Atzeni
authors.forename: Olivier
authors.initials: O
authors.lastname: Degoul
authors.forename: Aurélie
authors.initials: A
authors.lastname: Pagnon-Minot
authors.forename: Daniel
authors.initials: D
authors.lastname: Hartmann
authors.forename: Ivan
authors.initials: I
authors.lastname: Martin
authors.forename: Arnaud
authors.initials: A
authors.lastname: Scherberich
authors.forename: Colin
authors.initials: C
authors.lastname: McGuckin
mesh_terms: D000818:Animals; D001706:Biopsy; D002454:Cell Differentiation; D002478:Cells, Cultured; D016895:Culture Media, Serum-Free; D005260:Female; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D051379:Mice; D010006:Osteoblasts / Q000166:cytology*; D010012:Osteogenesis
chemical_list: D016895:Culture Media, Serum-Free