title: Mechanical Stimulation Increases Knee Meniscus Gene RNA-level Expression in Adipose-derived Stromal Cells.
abstract: Efforts have been made to engineer knee meniscus tissue for injury repair, yet most attempts have been unsuccessful. Creating a cell source that resembles the complex, heterogeneous phenotype of the meniscus cell remains difficult. Stem cell differentiation has been investigated, mainly using bone marrow mesenchymal cells and biochemical means for differentiation, resulting in no solution. Mechanical stimulation has been investigated to an extent with no conclusion. Here, we explore the potential for and effectiveness of mechanical stimulation to induce the meniscal phenotype in adipose-derived stromal cells.
  
  
  METHODS
  Human adipose-derived stromal cells were chosen for their fibrogenic nature and conduciveness for chondrogenesis. Biochemical and mechanical stimulation were investigated. Biochemical stimulation included fibrogenic and chondrogenic media. For mechanical stimulation, a custom-built device was used to apply constant, cyclical, uniaxial strain for up to 6 hours. Strain and frequency varied.
  
  
  RESULTS
  Under biochemical stimulation, both fibrogenic (collagen I, versican) and chondrogenic (collagen II, Sox9, aggrecan) genes were expressed by cells exposed to either fibrogenic or chondrogenic biochemical factors. Mechanical strain was found to preferentially promote fibrogenesis over chondrogenesis, confirming that tensile strain is an effective fibrogenic cue. Three hours at 10% strain and 1 Hz in chondrogenic media resulted in the highest expression of fibrochondrogenic genes. Although mechanical stimulation did not seem to affect protein level expression, biochemical means did affect protein level presence of collagen fibers.
  
  
  CONCLUSIONS
  Mechanical stimulation can be a useful differentiation tool for mechanoresponsive cell types as long as biochemical factors are also integrated.
authors.affiliation: Department of Biomedical Engineering, Wayne State University, Detroit, Mich.; Department of Plastic Surgery, Henry Ford Health System, Detroit, Mich.; and Hagey Laboratory for Pediatric Regenerative Medicine, Department of Surgery, Plastic and Reconstructive Surgery, Stanford University School of Medicine, Stanford, Calif.
authors.forename: Elizabeth M
authors.initials: EM
authors.lastname: Meier
authors.affiliation: Department of Biomedical Engineering, Wayne State University, Detroit, Mich.; Department of Plastic Surgery, Henry Ford Health System, Detroit, Mich.; and Hagey Laboratory for Pediatric Regenerative Medicine, Department of Surgery, Plastic and Reconstructive Surgery, Stanford University School of Medicine, Stanford, Calif.
authors.forename: Bin
authors.initials: B
authors.lastname: Wu
authors.affiliation: Department of Biomedical Engineering, Wayne State University, Detroit, Mich.; Department of Plastic Surgery, Henry Ford Health System, Detroit, Mich.; and Hagey Laboratory for Pediatric Regenerative Medicine, Department of Surgery, Plastic and Reconstructive Surgery, Stanford University School of Medicine, Stanford, Calif.
authors.forename: Aamir
authors.initials: A
authors.lastname: Siddiqui
authors.affiliation: Department of Biomedical Engineering, Wayne State University, Detroit, Mich.; Department of Plastic Surgery, Henry Ford Health System, Detroit, Mich.; and Hagey Laboratory for Pediatric Regenerative Medicine, Department of Surgery, Plastic and Reconstructive Surgery, Stanford University School of Medicine, Stanford, Calif.
authors.forename: Donna G
authors.initials: DG
authors.lastname: Tepper
authors.affiliation: Department of Biomedical Engineering, Wayne State University, Detroit, Mich.; Department of Plastic Surgery, Henry Ford Health System, Detroit, Mich.; and Hagey Laboratory for Pediatric Regenerative Medicine, Department of Surgery, Plastic and Reconstructive Surgery, Stanford University School of Medicine, Stanford, Calif.
authors.forename: Michael T
authors.initials: MT
authors.lastname: Longaker
authors.affiliation: Department of Biomedical Engineering, Wayne State University, Detroit, Mich.; Department of Plastic Surgery, Henry Ford Health System, Detroit, Mich.; and Hagey Laboratory for Pediatric Regenerative Medicine, Department of Surgery, Plastic and Reconstructive Surgery, Stanford University School of Medicine, Stanford, Calif.
authors.forename: Mai T
authors.initials: MT
authors.lastname: Lam