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In Vitro Expansion of Corneal Endothelial Cells on Biomimetic Substrates

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  • Alternative Title:
    Sci Rep
  • Personal Author:
  • Description:
    Corneal endothelial (CE) cells do not divide in vivo, leading to edema, corneal clouding and vision loss when the density drops below a critical level. The endothelium can be replaced by transplanting allogeneic tissue; however, access to donated tissue is limited worldwide resulting in critical need for new sources of corneal grafts. In vitro expansion of CE cells is a potential solution, but is challenging due to limited proliferation and loss of phenotype in vitro via endothelial to mesenchymal transformation (EMT) and senescence. We hypothesized that a bioengineered substrate recapitulating chemo-mechanical properties of Descemet's membrane would improve the in vitro expansion of CE cells while maintaining phenotype. Results show that bovine CE cells cultured on a polydimethylsiloxane surface with elastic modulus of 50 kPa and collagen IV coating achieved >3000-fold expansion. Cells grew in higher-density monolayers with polygonal morphology and ZO-1 localization at cell-cell junctions in contrast to control cells on polystyrene that lost these phenotypic markers coupled with increased α-smooth muscle actin expression and fibronectin fibril assembly. In total, these results demonstrate that a biomimetic substrate presenting native basement membrane ECM proteins and mechanical environment may be a key element in bioengineering functional CE layers for potential therapeutic applications.
  • Subjects:
  • Source:
    Sci Rep. 2015; 5.
  • Pubmed ID:
    25609008
  • Pubmed Central ID:
    PMC4302312
  • Document Type:
    Journal Article
  • Funding:
    DP2HL117750/DP/NCCDPHP CDC HHS/United States
  • Volume:
    5
  • Collection(s):
  • Main Document Checksum:
    urn:sha256:37521f03bf97772d43b81107d314341f8940b41a7f3475cee3e103aef847c2c5
  • Download URL:
  • File Type:
    Filetype[PDF - 1.65 MB ]
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