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

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.

Microgrooved collagen-based corneal scaffold for promoting collective cell migration and antifibrosis

“…18 Therefore, it's important to introduce topographic cues into corneal tissue engineering for mimicking the microenvironment of cells. Previous studies have shown that the engineering substrate topography can signicantly inuence cell shape, 19,20 adhesion, [21][22][23] migration, 24 proliferation, [25][26][27] and differentiation. 28,29 For corneal cells, their behaviors are also regulated by surface topography.…”

Combined analyses of RNA-sequence and Hi-C along with GWAS loci—A novel approach to dissect keloid disorder genetic mechanism

“…The experimental protocol was approved by the Ethics Committee of Shanghai Ninth People’s Hospital. As previously reported [ 60 ], the keloid tissues of inflammatory outer zone were excised and the epidermis was removed. The remaining dermis was cut into small fragments and digested with 0.3% collagenase (SERA, Heidelberg, Germany) in Dulbecco’s modified Eagle’s medium (DMEM) (Hyclone, Logan City, UT) for 6 h at 37°C on a rotator.…”

Clinical Challenge and Call for Research on Keloid Disorder: Meeting Report from The 3rd International Keloid Research Foundation Symposium, Beijing 2019

“…The elongated cells gradually lost their fibrotic phenotype with reduced cell proliferation and cell cycle arrest in Sphase. These changes were accompanied with reduced expression of fibrotic markers, such as collagen, fibronectin, asmooth muscle actin and transforming growth factor-b1, along with attenuated SMAD and extracellular signal-regulated kinase phosphorylation levels (Huang, 2019).…”

“…The cellular topography as a modifying factor of cell behavior was further investigated in a study were keloid fibroblasts were cultured on a surface with parallel microgrooves (Huang, 2019). In particular, growing cells in grooves with 3-mm depth and 10-mm width resulted in significant elongation and alignment of the cultured cells with reduced nuclear area.…”