Nonviral gene transfer into human meniscal cells. Part II: effect of three-dimensional environment and overexpression of human fibroblast growth factor 2

Int Orthop. 2014 Sep;38(9):1931-6. doi: 10.1007/s00264-014-2405-z. Epub 2014 Jun 24.

Abstract

Purpose: Our aim was to study the effect of three-dimensional (3D) environment and overexpression of human fibroblast growth factor 2 (FGF-2) on meniscal fibrochondrocytes in vitro.

Methods: Human meniscal fibrochondrocytes were transfected with expression plasmid vectors carrying the Photinus pyralis luciferase gene, the Escherichia coli β-galactosidase gene or a human FGF-2 cDNA. Modified fibrochondrocytes were cultivated in 3D alginate hydrogel or cell pellets or in 2D monolayer culture.

Results: The levels of luciferase activity showed a peak at day two and returned to baseline levels by day 11, regardless of the type of cultivation. Both 3D environments supported the secretion of human FGF-2 protein upon FGF-2 transfection. Overexpression of human FGF-2 by genetically modified human meniscal fibrochondrocytes stimulated proliferation but not glycosaminoglycan synthesis only in 3D culture. Culture in alginate spheres resulted in a larger difference in cell numbers compared with pellet cultures.

Conclusions: Three-dimensional alginate spheres are well suited for the culture of genetically modified human meniscal fibrochondrocytes. These data are of value for cell-based approaches to meniscal repair using genetically modified human meniscal fibrochondrocytes overexpressing human FGF-2.

MeSH terms

  • Alginates
  • Animals
  • Cell Culture Techniques / methods*
  • Cell Survival
  • Cell Transplantation / methods*
  • Cells, Cultured
  • Chondrocytes / cytology
  • Chondrocytes / metabolism
  • Chondrocytes / transplantation*
  • Escherichia coli / genetics
  • Fibroblast Growth Factor 2 / genetics
  • Fibroblast Growth Factor 2 / metabolism*
  • Fireflies / genetics
  • Gene Transfer Techniques*
  • Genetic Therapy / methods
  • Genetic Vectors
  • Glucuronic Acid
  • Hexuronic Acids
  • Humans
  • In Vitro Techniques
  • Menisci, Tibial / cytology
  • Menisci, Tibial / metabolism
  • Menisci, Tibial / surgery*
  • Up-Regulation

Substances

  • Alginates
  • Hexuronic Acids
  • Fibroblast Growth Factor 2
  • Glucuronic Acid