Aligned topography mediated cell elongation reverses pathological phenotype of in vitro cultured keloid fibroblasts

J Biomed Mater Res A. 2019 Jul;107(7):1366-1378. doi: 10.1002/jbm.a.36650. Epub 2019 Feb 28.

Abstract

Topography modified cell behavior remains less explored in diseased cells. This study investigated the reversing effect on the pathological phenotype of keloid fibroblasts via culturing cells on a parallel microgrooved surface. The results showed that this particular topography with 3 μm groove depth and 10 μm width could significantly elongate and align the cultured cells with reduced cell (nucleus) area and increased cell (nucleus) body aspect ratio and cell (nucleus) body major axis (p < 0.05). Importantly, the elongated cells gradually lost their fibrotic phenotype with inhibited cell proliferation and cell cycle arrest in S-phase (p < 0.05), reduced expression of fibrotic markers such as collagen, fibronectin, connective tissue growth factor, α-smooth muscle actin, transforming growth factor-β1 (p < 0.05), and increased matrix metalloproteinases/tissue inhibitor-1 ratio (p < 0.05) along with attenuated Smad and Erk phosphorylation level. All these indicate that this parallel topography is powerful enough to modify keloid cell phenotype, a benign skin tumor with excessive cell proliferation and matrix production. © 2019 Wiley Periodicals, Inc. J Biomed Mater Res Part A, 2019.

Keywords: aligned topography; elongated cell morphology; keloid fibroblasts; phenotype reversion.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Cell Cycle Checkpoints
  • Cell Proliferation
  • Cells, Cultured
  • Child
  • Extracellular Matrix / metabolism
  • Female
  • Fibroblasts / metabolism
  • Fibroblasts / pathology*
  • Gene Expression Regulation
  • Humans
  • Keloid / genetics
  • Keloid / pathology*
  • Male
  • Middle Aged
  • Phenotype
  • Recombinant Proteins / metabolism
  • S Phase
  • Signal Transduction
  • Skin / pathology
  • Transforming Growth Factor beta1 / genetics
  • Transforming Growth Factor beta1 / metabolism
  • Transforming Growth Factor beta3 / genetics
  • Transforming Growth Factor beta3 / metabolism
  • Young Adult

Substances

  • Recombinant Proteins
  • TGFB1 protein, human
  • TGFB3 protein, human
  • Transforming Growth Factor beta1
  • Transforming Growth Factor beta3