title: Regionally-derived cell populations and skeletal stem cells from human foetal femora exhibit specific osteochondral and multi-lineage differentiation capacity in vitro and ex vivo.
abstract: BACKGROUND
  Adult skeletal stem cells (SSCs) often exhibit limited in vitro expansion with undesirable phenotypic changes and loss of differentiation capacity. Foetal tissues offer an alternative cell source, providing SSCs which exhibit desirable differentiation capacity over prolonged periods, ideal for extensive in vitro and ex vivo investigation of fundamental bone biology and skeletal development.
  
  
  METHODS
  We have examined the derivation of distinct cell populations from human foetal femora. Regionally isolated populations including epiphyseal and diaphyseal cells were carefully dissected. Expression of the SSC marker Stro-1 was also found in human foetal femora over a range of developmental stages and subsequently utilised for immuno-selection.
  
  
  RESULTS
  Regional populations exhibited chondrogenic (epiphyseal) and osteogenic (diaphyseal) phenotypes following in vitro and ex vivo characterisation and molecular analysis, indicative of native SSC maturation during skeletal development. However, each population exhibited potential for induced multi-lineage differentiation towards bone (bone nodule formation), cartilage (proteoglycan and mucopolysaccharide deposition) and fat (lipid deposition), suggesting the presence of a shared stem cell sub-population. This shared sub-population may be comprised of Stro-1+ cells, which were later identified and immuno-selected from whole foetal femora exhibiting multi-lineage differentiation capacity in vitro and ex vivo.
  
  
  CONCLUSIONS
  Distinct populations were isolated from human foetal femora expressing osteochondral differentiation capacity. Stro-1 immuno-selected SSCs were isolated from whole femora expressing desirable multi-lineage differentiation capacity over prolonged in vitro expansion, superior to their adult-derived counterparts, providing a valuable cell source with which to study bone biology and skeletal development.
authors.affiliation: Bone and Joint Research Group, Centre for Human Development, Stem Cells and Regeneration, Human Development and Health, University of Southampton, School of Medicine, Institute of DevelopmentalSciences, Mail Point 887, Southampton General Hospital, Tremona Road, Southampton, SO16 6YD, UK. d.gothard@hotmail.co.uk.
authors.forename: David
authors.initials: D
authors.lastname: Gothard
authors.affiliation: Bone and Joint Research Group, Centre for Human Development, Stem Cells and Regeneration, Human Development and Health, University of Southampton, School of Medicine, Institute of DevelopmentalSciences, Mail Point 887, Southampton General Hospital, Tremona Road, Southampton, SO16 6YD, UK. kc81@me.com.
authors.forename: Kelvin
authors.initials: K
authors.lastname: Cheung
authors.affiliation: Bone and Joint Research Group, Centre for Human Development, Stem Cells and Regeneration, Human Development and Health, University of Southampton, School of Medicine, Institute of DevelopmentalSciences, Mail Point 887, Southampton General Hospital, Tremona Road, Southampton, SO16 6YD, UK. J.Kanczler@soton.ac.uk.
authors.forename: Janos M
authors.initials: JM
authors.lastname: Kanczler
authors.affiliation: Centre for Human Development, Stem Cells and Regeneration, Human Development and Health, University of Southampton, School of Medicine, Institute of Developmental Sciences, Mail Point 887, Southampton General Hospital, Tremona Road, Southampton, SO16 6YD, UK. D.I.Wilson@soton.ac.uk.|University Hospital Southampton NHS Foundation Trust, Tremona Road, SO16 6YD, Southampton, UK. D.I.Wilson@soton.ac.uk.
authors.forename: David I
authors.initials: DI
authors.lastname: Wilson
authors.affiliation: Bone and Joint Research Group, Centre for Human Development, Stem Cells and Regeneration, Human Development and Health, University of Southampton, School of Medicine, Institute of DevelopmentalSciences, Mail Point 887, Southampton General Hospital, Tremona Road, Southampton, SO16 6YD, UK. roco@soton.ac.uk.
authors.forename: Richard O C
authors.initials: RO
authors.lastname: Oreffo
mesh_terms: D050156:Adipogenesis; D000818:Animals; D000954:Antigens, Surface / Q000378:metabolism; D001861:Bone Regeneration; D002454:Cell Differentiation; D002469:Cell Separation; D002642:Chick Embryo; D020219:Chondrogenesis; D018483:Diaphyses / Q000166:cytology; D004838:Epiphyses / Q000166:cytology; D005269:Femur / Q000166:cytology / Q000196:embryology; D053686:Fetal Stem Cells / Q000166:cytology* / Q000502:physiology; D005333:Fetus / Q000166:cytology; D006801:Humans; D066298:In Vitro Techniques; D032448:Myoblasts, Skeletal / Q000166:cytology* / Q000502:physiology; D010012:Osteogenesis
chemical_list: D000954:Antigens, Surface; C525591:STRO-1 antigen, human