title: Pretreatment with IL-1β enhances proliferation and chondrogenic potential of synovium-derived mesenchymal stem cells.
abstract: Synovial mesenchymal stem cells (MSCs) are an attractive cell source for cartilage regeneration because of their high proliferative ability and chondrogenic potential. We have performed clinical trials using synovial MSCs to regenerate articular cartilage. To achieve good clinical outcomes for cell transplantation therapy, it is important to control both quantity (cell number) and quality (pluripotency or chondrogenic potential) of the cells for transplantation. Interleukin (IL)-1β is a pro-inflammatory cytokine with significant pro-proliferative potential for mesenchymal cells. However, the effects of IL-1β on synovial MSCs remain unknown. We investigated the effects of pretreatment with IL-1β on synovial MSCs.
  
  
  
  Human synovial tissue was harvested during total knee arthroplasty. Nucleated cells were plated and cultured in the absence or presence of IL-1β at 10-13, 10-12, 10-11, 10-10, 10-9or 10-8g/mL for 14 days.
  
  
  
  The number of synovial MSCs increased in a concentration-dependent manner. When cultured for 21 days in chondrogenic medium after pretreatment with 10-8g/mL IL-1β, pellet aggregation was observed, whereas pretreatment with 10-12, 10-11or 10-10g/mL IL-1β significantly increased the weight of cartilage pellets (P <0.01). Surface markers for adhesion ability and pluripotency were reduced with high concentrations of IL-1β. IL-6 and IL-8 expression increased, but no changes in the expression level of growth factors were indicated by cytokine array.
  
  
  
  We have demonstrated that pretreatment of IL-1β increased the proliferation and chondrogenic potential of synovial MSCs, which may promote the regenerative potential of synovial MSCs.
authors.affiliation: Department of Joint Surgery and Sports Medicine, Tokyo Medical and Dental University, Tokyo, Japan.
authors.forename: Etsuko
authors.initials: E
authors.lastname: Matsumura
authors.affiliation: Department of Cartilage Regeneration, Tokyo Medical and Dental University, Tokyo, Japan.
authors.forename: Kunikazu
authors.initials: K
authors.lastname: Tsuji
authors.affiliation: Center for Stem Cell and Regenerative Medicine, Tokyo Medical and Dental University, Tokyo, Japan.
authors.forename: Keiichiro
authors.initials: K
authors.lastname: Komori
authors.affiliation: Department of Joint Surgery and Sports Medicine, Tokyo Medical and Dental University, Tokyo, Japan.
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Koga
authors.affiliation: Center for Stem Cell and Regenerative Medicine, Tokyo Medical and Dental University, Tokyo, Japan.
authors.forename: Ichiro
authors.initials: I
authors.lastname: Sekiya
authors.affiliation: Department of Joint Surgery and Sports Medicine, Tokyo Medical and Dental University, Tokyo, Japan. Electronic address: muneta.orj@tmd.ac.jp.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Muneta
mesh_terms: D002358:Cartilage, Articular / Q000166:cytology; D002454:Cell Differentiation / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects*; D002478:Cells, Cultured; D020219:Chondrogenesis / Q000187:drug effects*; D005260:Female; D006801:Humans; D053583:Interleukin-1beta / Q000494:pharmacology*; D015850:Interleukin-6 / Q000378:metabolism; D016209:Interleukin-8 / Q000378:metabolism; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D008875:Middle Aged; D013583:Synovial Membrane / Q000166:cytology*
chemical_list: D053583:Interleukin-1beta; D015850:Interleukin-6; D016209:Interleukin-8
keywords: cell proliferation; cell transplantation therapy; chondrogenesis; interleukin-1beta (IL-1β); synovial mesenchymal stem cells (MSCs)