Bifunctional Hydrogels Containing the Laminin Motif IKVAV Promote Neurogenesis

Stem Cell Reports. 2017 Nov 14;9(5):1432-1440. doi: 10.1016/j.stemcr.2017.09.002. Epub 2017 Oct 5.

Abstract

Engineering of biomaterials with specific biological properties has gained momentum as a means to control stem cell behavior. Here, we address the effect of bifunctionalized hydrogels comprising polylysine (PL) and a 19-mer peptide containing the laminin motif IKVAV (IKVAV) on embryonic and adult neuronal progenitor cells under different stiffness regimes. Neuronal differentiation of embryonic and adult neural progenitors was accelerated by adjusting the gel stiffness to 2 kPa and 20 kPa, respectively. While gels containing IKVAV or PL alone failed to support long-term cell adhesion, in bifunctional gels, IKVAV synergized with PL to promote differentiation and formation of focal adhesions containing β1-integrin in embryonic cortical neurons. Furthermore, in adult neural stem cell culture, bifunctionalized gels promoted neurogenesis via the expansion of neurogenic clones. These data highlight the potential of synthetic matrices to steer stem and progenitor cell behavior via defined mechano-adhesive properties.

Keywords: IKVAV; bioengineering; biomaterials; cell differentiation; hydrogels; laminin; neural stem cells; neurogenesis; polylysine; β(1)-integrin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cells, Cultured
  • Elasticity
  • Focal Adhesions / metabolism
  • Hydrogels / chemistry
  • Hydrogels / pharmacology*
  • Laminin / chemistry*
  • Laminin / pharmacology
  • Mice
  • Mice, Inbred C57BL
  • Mouse Embryonic Stem Cells / cytology
  • Mouse Embryonic Stem Cells / drug effects
  • Neural Stem Cells / cytology*
  • Neural Stem Cells / drug effects
  • Neurogenesis*
  • Peptide Fragments / chemistry*
  • Peptide Fragments / pharmacology
  • Polylysine / chemistry
  • Polylysine / pharmacology
  • Tissue Engineering / methods

Substances

  • Hydrogels
  • Laminin
  • Peptide Fragments
  • isoleucyl-lysyl-valyl-alanyl-valine
  • Polylysine