Introduction of N-cadherin-binding motif to alginate hydrogels for controlled stem cell differentiation

Colloids Surf B Biointerfaces. 2017 Jul 1:155:229-237. doi: 10.1016/j.colsurfb.2017.04.014. Epub 2017 Apr 9.

Abstract

Control of stem cell fate and phenotype using biomimetic synthetic extracellular matrices (ECMs) is an important tissue engineering approach. Many studies have focused on improving cell-matrix interactions. However, proper control of cell-cell interactions using synthetic ECMs could be critical for tissue engineering, especially with undifferentiated stem cells. In this study, alginate hydrogels were modified with a peptide derived from the low-density lipoprotein receptor-related protein 5 (LRP5), which is known to bind to N-cadherin, as a cell-cell interaction motif. In vitro changes in the morphology and differentiation of mouse bone marrow stromal cells (D1 stem cells) cultured in LRP5-alginate hydrogels were investigated. LRP5-alginate gels successfully induced stem cell aggregation and enhanced chondrogenic differentiation of D1 stem cells, compared to RGD-alginate gels, at low cell density. This approach to tailoring synthetic biomimetic ECMs using cell-cell interaction motifs may be critical in tissue engineering approaches using stem cells.

Keywords: Alginate hydrogel; Cell-cell interaction; Low-density lipoprotein receptor-related protein 5; N-cadherin; Stem cell.

MeSH terms

  • Alginates / chemistry*
  • Amino Acid Sequence
  • Animals
  • Biomimetic Materials / chemistry
  • Biomimetic Materials / pharmacology*
  • Cadherins / genetics
  • Cadherins / metabolism
  • Carbodiimides / chemistry
  • Cell Communication
  • Cell Culture Techniques
  • Cell Differentiation / drug effects
  • Cell Line
  • Chondrocytes / drug effects*
  • Chondrocytes / metabolism
  • Chondrogenesis / drug effects
  • Extracellular Matrix / chemistry
  • Gene Expression
  • Glucuronic Acid / chemistry
  • Hexuronic Acids / chemistry
  • Hydrogels / chemistry
  • Hydrogels / pharmacology*
  • Low Density Lipoprotein Receptor-Related Protein-5 / genetics
  • Low Density Lipoprotein Receptor-Related Protein-5 / metabolism
  • Mesenchymal Stem Cells / drug effects*
  • Mesenchymal Stem Cells / metabolism
  • Mice
  • Peptides / chemical synthesis
  • Peptides / pharmacology*
  • Tissue Engineering / methods
  • Tissue Scaffolds

Substances

  • 1-ethyl-3-(3-(diethylamino)propyl)carbodiimide
  • Alginates
  • Cadherins
  • Carbodiimides
  • Cdh2 protein, mouse
  • Hexuronic Acids
  • Hydrogels
  • Low Density Lipoprotein Receptor-Related Protein-5
  • Lrp5 protein, mouse
  • Peptides
  • Glucuronic Acid