Influence of culture conditions and extracellular matrix alignment on human mesenchymal stem cells invasion into decellularized engineered tissues

Nathan K. Weidenhamer, Dusty L. Moore, Fluvio L. Lobo, Nathaniel T. Klair, Robert T. Tranquillo

Research output: Contribution to journalArticlepeer-review

12 Scopus citations

Abstract

The variables that influence the in vitro recellularization potential of decellularized engineered tissues, such as cell culture conditions and scaffold alignment, have yet to be explored. The goal of this work was to explore the influence of insulin and ascorbic acid and extracellular matrix (ECM) alignment on the recellularization of decellularized engineered tissue by human mesenchymal stem cells (hMSCs). Aligned and non-aligned tissues were created by specifying the geometry and associated mechanical constraints to fibroblast-mediated fibrin gel contraction and remodelling using circular and C-shaped moulds. Decellularized tissues (matrices) of the same alignment were created by decellularization with detergents. Ascorbic acid promoted the invasion of hMSCs into the matrices due to a stimulated increase in motility and proliferation. Invasion correlated with hyaluronic acid secretion, α-smooth muscle actin expression and decreased matrix thickness. Furthermore, hMSCs invasion into aligned and non-aligned matrices was not different, although there was a difference in cell orientation. Finally, we show that hMSCs on the matrix surface appear to differentiate toward a smooth muscle cell or myofibroblast phenotype with ascorbic acid treatment. These results inform the strategy of recellularizing decellularized engineered tissue with hMSCs.

Original languageEnglish (US)
Pages (from-to)605-618
Number of pages14
JournalJournal of Tissue Engineering and Regenerative Medicine
Volume9
Issue number5
DOIs
StatePublished - May 1 2015

Bibliographical note

Publisher Copyright:
© 2014 John Wiley & Sons, Ltd.

Keywords

  • Alignment
  • Cell differentiation
  • Cell invasion
  • Decellularization
  • Extracellular matrix
  • Mesenchymal stem cell

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