title: Gene expression profiling of human mesenchymal stem cells derived from bone marrow during expansion and osteoblast differentiation.
abstract: BACKGROUND
  Human mesenchymal stem cells (MSC) with the capacity to differentiate into osteoblasts provide potential for the development of novel treatment strategies, such as improved healing of large bone defects. However, their low frequency in bone marrow necessitate ex vivo expansion for further clinical application. In this study we asked if MSC are developing in an aberrant or unwanted way during ex vivo long-term cultivation and if artificial cultivation conditions exert any influence on their stem cell maintenance. To address this question we first developed human oligonucleotide microarrays with 30.000 elements and then performed large-scale expression profiling of long-term expanded MSC and MSC during differentiation into osteoblasts.
  
  
  RESULTS
  The results showed that MSC did not alter their osteogenic differentiation capacity, surface marker profile, and the expression profiles of MSC during expansion. Microarray analysis of MSC during osteogenic differentiation identified three candidate genes for further examination and functional analysis: ID4, CRYAB, and SORT1. Additionally, we were able to reconstruct the three developmental phases during osteoblast differentiation: proliferation, matrix maturation, and mineralization, and illustrate the activation of the SMAD signaling pathways by TGF-beta2 and BMPs.
  
  
  CONCLUSIONS
  With a variety of assays we could show that MSC represent a cell population which can be expanded for therapeutic applications.
authors.affiliation: Institute for Genomics and Bioinformatics and Christian-Doppler Laboratory for Genomics and Bioinformatics, Graz University of Technology, Graz, Austria. birgit.kulterer@gmx.at <birgit.kulterer@gmx.at>
authors.forename: Birgit
authors.initials: B
authors.lastname: Kulterer
authors.forename: Gerald
authors.initials: G
authors.lastname: Friedl
authors.forename: Anita
authors.initials: A
authors.lastname: Jandrositz
authors.forename: Fatima
authors.initials: F
authors.lastname: Sanchez-Cabo
authors.forename: Andreas
authors.initials: A
authors.lastname: Prokesch
authors.forename: Christine
authors.initials: C
authors.lastname: Paar
authors.forename: Marcel
authors.initials: M
authors.lastname: Scheideler
authors.forename: Reinhard
authors.initials: R
authors.lastname: Windhager
authors.forename: Karl-Heinz
authors.initials: KH
authors.lastname: Preisegger
authors.forename: Zlatko
authors.initials: Z
authors.lastname: Trajanoski
mesh_terms: D001854:Bone Marrow Cells / Q000166:cytology / Q000378:metabolism*; D002454:Cell Differentiation / Q000235:genetics*; D016000:Cluster Analysis; D003114:Colony-Forming Units Assay; D020869:Gene Expression Profiling / Q000379:methods*; D006801:Humans; D051796:Inhibitor of Differentiation Proteins / Q000235:genetics; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D010006:Osteoblasts / Q000166:cytology / Q000378:metabolism*; D010012:Osteogenesis / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D038203:alpha-Crystallin B Chain / Q000235:genetics
chemical_list: C059215:CRYAB protein, human; C490128:ID4 protein, human; D051796:Inhibitor of Differentiation Proteins; D038203:alpha-Crystallin B Chain