title: Effect of Short-Term Stimulation with Interleukin-1β and Differentiation Medium on Human Mesenchymal Stromal Cell Paracrine Activity in Coculture with Osteoblasts.
abstract: BACKGROUND
  Human mesenchymal stromal cells (hMSCs) exhibit the potential to accelerate bone healing by enhanced osteogenic differentiation. Interleukin-1β is highly expressed during fracture healing and has been demonstrated to exert a significant impact on the differentiation behaviour of hMSCs. Here, we investigate the effect of 2-hour IL-1β stimulation on the differentiation and paracrine activity of hMSCs in coculture with osteosarcoma cells in vitro.
  
  
  METHODS
  hMSCs from 3 donors were incubated for 2 hours with 10 ng/mL IL-1β and subsequently cocultured with MG63-GFP cells either in control or in differentiation medium in a transwell system for 28 days. Genetic and functional effects were investigated.
  
  
  RESULTS
  hMSCs cultured in control medium exhibited a regulatory effect on cocultured MG63-GFP cells, resulting in upregulation of osteogenic gene expression in combination with increased ALP activity. However, while stimulated hMSCs cultured under differentiation conditions exhibit signs of osteogenic differentiation, osteogenic differentiation also caused an impaired regulatory effect on the cocultured MG63-GFP cells.
  
  
  CONCLUSIONS
  Short stimulation of hMSCs has the potential to modify their long-term behaviour. In addition, undifferentiated hMSCs are able to regulate osteoblast differentiation; however, this regulatory function is lost upon osteogenic differentiation in vitro. This offers a novel approach for clinical cell therapy protocols.
authors.affiliation: AO Research Institute Davos, 7270 Davos Platz, Switzerland; Department of Oral and Maxillofacial Surgery/Clinical Navigation, Charité-Universitätsmedizin Berlin, Campus Virchow-Clinic, 13353 Berlin, Germany.
authors.forename: Jan O
authors.initials: JO
authors.lastname: Voss
authors.affiliation: AO Research Institute Davos, 7270 Davos Platz, Switzerland.
authors.forename: Claudia
authors.initials: C
authors.lastname: Loebel
authors.affiliation: AO Research Institute Davos, 7270 Davos Platz, Switzerland.
authors.forename: Jennifer J
authors.initials: JJ
authors.lastname: Bara
authors.affiliation: AO Research Institute Davos, 7270 Davos Platz, Switzerland; Department of Oral and Maxillofacial Surgery, Medical Center-University of Freiburg, 79106 Freiburg, Germany.
authors.forename: Marc Anton
authors.initials: MA
authors.lastname: Fussinger
authors.affiliation: Department of Oral and Maxillofacial Surgery, Medical Center-University of Freiburg, 79106 Freiburg, Germany.
authors.forename: Fabian
authors.identifier: 0000-0002-6452-7560
authors.initials: F
authors.lastname: Duttenhoefer
authors.affiliation: AO Research Institute Davos, 7270 Davos Platz, Switzerland.
authors.forename: Mauro
authors.initials: M
authors.lastname: Alini
authors.affiliation: AO Research Institute Davos, 7270 Davos Platz, Switzerland.
authors.forename: Martin J
authors.initials: MJ
authors.lastname: Stoddart
mesh_terms: D000328:Adult; D002454:Cell Differentiation / Q000187:drug effects*; D045744:Cell Line, Tumor; D018920:Coculture Techniques; D003470:Culture Media; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D053583:Interleukin-1beta / Q000494:pharmacology*; D008297:Male; D059630:Mesenchymal Stem Cells / Q000378:metabolism*; D008875:Middle Aged; D010006:Osteoblasts / Q000378:metabolism*; D010012:Osteogenesis / Q000187:drug effects; D012516:Osteosarcoma / Q000378:metabolism; D019899:Paracrine Communication / Q000187:drug effects*; D013997:Time Factors
chemical_list: D003470:Culture Media; C508585:IL1B protein, human; D053583:Interleukin-1beta