title: Bidirectional and mutually beneficial interactions between human mesenchymal stem cells and osteoarthritic chondrocytes in micromass co-cultures.
abstract: OBJECTIVE
  Mesenchymal stem cell (MSC)-based therapy presents a promising approach for treating osteoarthritis (OA). However, the molecular interactions between MSCs and OA chondrocytes (OACs) are not known. This study aims to investigate the bidirectional interactions between human MSCs (hMSCs) and human OACs (hOACs) in a 3D co-culture system.
  
  
  METHODS
  hMSC-collagen microspheres were cultured in hOAC-conditioned medium or co-cultured with hOAC-collagen microspheres. Growth characteristics, glycosaminoglycan (GAG) production, gene expression of major OA-associated chondrogenic markers, including SOX9, COL2A1, ACAN and MMP13, were investigated in both cell types.
  
  
  RESULTS
  Both the conditioned medium and the co-culture induced MSC chondrogenesis with enhanced GAG production, SOX9 gene and protein expression, and gene expression of ACAN and COL2A1. Meanwhile, the co-culture also induced hOACs to partially resume the lost chondrogenic phenotype as shown by reduced proliferation, enhanced GAG production when hMSCs were chondrogenically predifferentiated, and reduced MMP13 gene expression.
  
  
  CONCLUSIONS
  This work suggests that 3D co-culture of hMSCs and hOACs is mutually beneficial to each other, suggesting the potential therapeutic effect of delivering hMSC in scaffolds directly to OA defects.
authors.affiliation: Tissue Engineering Laboratory, Department of Mechanical Engineering, The University of Hong Kong, Pokfulam Road, Hong Kong Special Administrative Region, China.
authors.forename: Hua Jia
authors.initials: HJ
authors.lastname: Diao
authors.forename: Chui Wai
authors.initials: CW
authors.lastname: Yeung
authors.forename: Chun Hoi
authors.initials: CH
authors.lastname: Yan
authors.forename: Godfrey C F
authors.initials: GC
authors.lastname: Chan
authors.forename: Barbara P
authors.initials: BP
authors.lastname: Chan
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000378:metabolism; D002358:Cartilage, Articular / Q000473:pathology; D002450:Cell Communication; D049109:Cell Proliferation; D019902:Chondrocytes / Q000378:metabolism / Q000473:pathology*; D020219:Chondrogenesis / Q000235:genetics; D018920:Coculture Techniques; D005260:Female; D005455:Fluorescent Antibody Technique; D005786:Gene Expression Regulation; D006025:Glycosaminoglycans / Q000096:biosynthesis; D006801:Humans; D008297:Male; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000378:metabolism; D008863:Microspheres; D008875:Middle Aged; D010003:Osteoarthritis / Q000473:pathology*; D055758:SOX9 Transcription Factor / Q000378:metabolism
chemical_list: D015415:Biomarkers; D006025:Glycosaminoglycans; D055758:SOX9 Transcription Factor; C527932:SOX9 protein, human