title: Pre-Treatment of Human Mesenchymal Stem Cells With Inflammatory Factors or Hypoxia Does Not Influence Migration to Osteoarthritic Cartilage and Synovium.
abstract: BACKGROUND
  Mesenchymal stem cells (MSCs) are promising candidates as a cell-based therapy for osteoarthritis (OA), although current results are modest. Pre-treatment of MSCs before application might improve their therapeutic efficacy.
  
  
  OBJECTIVE
  Pre-treatment of MSCs with inflammatory factors or hypoxia will improve their migration and adhesion capacities toward OA-affected tissues.
  
  
  METHODS
  Controlled laboratory study.
  
  
  METHODS
  We used real-time polymerase chain reaction to determine the effects of different fetal calf serum (FCS) batches, platelet lysate (PL), hypoxia, inflammatory factors, factors secreted by OA tissues, and OA synovial fluid (SF) on the expression of 12 genes encoding chemokine or adhesion receptors. Migration of MSCs toward factors secreted by OA tissues was studied in vitro, and attachment of injected MSCs was evaluated in vivo in healthy and OA knees of male Wistar rats.
  
  
  RESULTS
  Different FCS batches, PL, or hypoxia did not influence the expression of the migration and adhesion receptor genes. Exposure to inflammatory factors altered the expression of CCR1, CCR4, CD44, PDGFRα, and PDGFRβ. MSCs migrated toward factors secreted by OA tissues in vitro. Neither pre-treatment with inflammatory factors nor the presence of OA influenced MSC migration in vitro or adhesion in vivo.
  
  
  CONCLUSIONS
  Factors secreted by OA tissues increase MSC migration in vitro. In vivo, no difference in MSC adhesion was found between OA and healthy knees. Pre-treatment with inflammatory factors influenced the expression of migration and adhesion receptors of MSCs but not their migration in vitro or adhesion in vivo.
  
  
  CONCLUSIONS
  To improve the therapeutic capacity of intra-articular injection of MSCs, they need to remain intra-articular for a longer period of time. Pre-treatment of MSCs with hypoxia or inflammatory factors did not increase the migration or adhesion capacity of MSCs and will therefore not likely prolong their intra-articular longevity. Alternative approaches to prolong the intra-articular presence of MSCs should be developed to increase the therapeutic effect of MSCs in OA.
authors.affiliation: Department of Orthopaedics, Erasmus MC Rotterdam, the Netherlands.|Department of Radiology, Erasmus MC Rotterdam, the Netherlands.
authors.forename: Maarten J C
authors.initials: MJ
authors.lastname: Leijs
authors.affiliation: Department of Orthopaedics, Erasmus MC Rotterdam, the Netherlands.
authors.forename: Gerben M
authors.initials: GM
authors.lastname: van Buul
authors.affiliation: Department of Orthopaedics, Erasmus MC Rotterdam, the Netherlands.
authors.forename: Jan A N
authors.initials: JA
authors.lastname: Verhaar
authors.affiliation: Department of Internal Medicine, Erasmus MC Rotterdam, the Netherlands.
authors.forename: Martin J
authors.initials: MJ
authors.lastname: Hoogduijn
authors.affiliation: Department of Orthopaedics, Erasmus MC Rotterdam, the Netherlands.
authors.forename: Pieter K
authors.initials: PK
authors.lastname: Bos
authors.affiliation: Department of Orthopaedics, Erasmus MC Rotterdam, the Netherlands.|Department of Otorhinolaryngology, Erasmus MC Rotterdam, the Netherlands.
authors.forename: Gerjo J V M
authors.initials: GJ
authors.lastname: van Osch
mesh_terms: D000368:Aged; D000693:Anaerobiosis; D000818:Animals; D002356:Cartilage / Q000187:drug effects / Q000378:metabolism; D002465:Cell Movement / Q000187:drug effects*; D002630:Chemotactic Factors / Q000378:metabolism*; D005260:Female; D006801:Humans; D018836:Inflammation Mediators / Q000008:administration & dosage*; D007270:Injections, Intra-Articular; D008297:Male; D059630:Mesenchymal Stem Cells / Q000187:drug effects / Q000378:metabolism*; D008875:Middle Aged; D020370:Osteoarthritis, Knee / Q000628:therapy*; D010100:Oxygen / Q000008:administration & dosage*; D051381:Rats; D017208:Rats, Wistar; D013583:Synovial Membrane / Q000187:drug effects / Q000378:metabolism
chemical_list: D002630:Chemotactic Factors; D018836:Inflammation Mediators; D010100:Oxygen
keywords: cell therapy; inflammation; mesenchymal stem cells; migration; osteoarthritis