Mechanical environment modulates biological properties of oligodendrocyte progenitor cells.

Anna Jagielska, Adele L Norman, Graeme Whyte, Krystyn J Van Vliet, Jochen Guck, Robin J M Franklin, Krystyn J Van Vliet

Research output: Contribution to journalArticle

58 Citations (Scopus)

Abstract

Myelination and its regenerative counterpart remyelination represent one of the most complex cell-cell interactions in the central nervous system (CNS). The biochemical regulation of axon myelination via the proliferation, migration, and differentiation of oligodendrocyte progenitor cells (OPCs) has been characterized extensively. However, most biochemical analysis has been conducted in vitro on OPCs adhered to substrata of stiffness that is orders of magnitude greater than that of the in vivo CNS environment. Little is known of how variation in mechanical properties over the physiological range affects OPC biology. Here, we show that OPCs are mechanosensitive. Cell survival, proliferation, migration, and differentiation capacity in vitro depend on the mechanical stiffness of polymer hydrogel substrata. Most of these properties are optimal at the intermediate values of CNS tissue stiffness. Moreover, many of these properties measured for cells on gels of optimal stiffness differed significantly from those measured on glass or polystyrene. The dependence of OPC differentiation on the mechanical properties of the extracellular environment provides motivation to revisit results obtained on nonphysiological, rigid surfaces. We also find that OPCs stiffen upon differentiation, but that they do not change their compliance in response to substratum stiffness, which is similar to embryonic stem cells, but different from adult stem cells. These results form the basis for further investigations into the mechanobiology of cell function in the CNS and may specifically shed new light on the failure of remyelination in chronic demyelinating diseases such as multiple sclerosis.
Original languageEnglish
Pages (from-to)2905-2914
Number of pages10
JournalStem Cells and Development
Volume21
Issue number16
DOIs
Publication statusPublished - Nov 2012

Keywords

  • Animals
  • Biological Markers
  • Biological Markers: metabolism
  • Biomechanics
  • Biomechanics: drug effects
  • Cell Adhesion
  • Cell Adhesion: drug effects
  • Cell Differentiation
  • Cell Differentiation: drug effects
  • Cell Lineage
  • Cell Lineage: drug effects
  • Cell Movement
  • Cell Movement: drug effects
  • Cell Proliferation
  • Cell Proliferation: drug effects
  • Cell Survival
  • Cell Survival: drug effects
  • Cellular Microenvironment
  • Cellular Microenvironment: drug effects
  • Hydrogels
  • Hydrogels: pharmacology
  • Oligodendroglia
  • Oligodendroglia: cytology
  • Oligodendroglia: drug effects
  • Oligodendroglia: metabolism
  • Polymers
  • Polymers: pharmacology
  • Rats
  • Sprague-Dawley
  • Stem Cells
  • Stem Cells: cytology
  • Stem Cells: drug effects
  • Stem Cells: metabolism

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  • Cite this

    Jagielska, A., Norman, A. L., Whyte, G., Van Vliet, K. J., Guck, J., Franklin, R. J. M., & Vliet, K. J. V. (2012). Mechanical environment modulates biological properties of oligodendrocyte progenitor cells. Stem Cells and Development, 21(16), 2905-2914. https://doi.org/10.1089/scd.2012.0189