Directional Topography Influences Adipose Mesenchymal Stromal Cell Plasticity: Prospects for Tissue Engineering and Fibrosis.

ABSTRACT: Introduction:Progenitor cells cultured on biomaterials with optimal physical-topographical properties respond with alignment and differentiation. Stromal cells from connective tissue can adversely differentiate to profibrotic myofibroblasts or favorably to smooth muscle cells (SMC). We hypothesized that myogenic differentiation of adipose tissue-derived stromal cells (ASC) depends on gradient directional topographic features. Methods:Polydimethylsiloxane (PDMS) samples with nanometer and micrometer directional topography gradients (wavelength (w) = 464-10, 990?nm; amplitude (a) = 49-3, 425?nm) were fabricated. ASC were cultured on patterned PDMS and stimulated with TGF-?1 to induce myogenic differentiation. Cellular alignment and adhesion were assessed by immunofluorescence microscopy after 24?h. After seven days, myogenic differentiation was examined by immunofluorescence microscopy, gene expression, and immunoblotting. Results:Cell alignment occurred on topographies larger than w = 1758?nm/a = 630?nm. The number and total area of focal adhesions per cell were reduced on topographies from w = 562?nm/a = 96?nm to w = 3919?nm/a = 1430?nm. Focal adhesion alignment was increased on topographies larger than w = 731?nm/a = 146?nm. Less myogenic differentiation of ASC occurred on topographies smaller than w = 784?nm/a = 209?nm. Conclusion:ASC adherence, alignment, and differentiation are directed by topographical cues. Our evidence highlights a minimal topographic environment required to facilitate the development of aligned and differentiated cell layers from ASC. These data suggest that nanotopography may be a novel tool for inhibiting fibrosis.

SUBMITTER: Liguori GR 

PROVIDER: S-EPMC6525798 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature