GFOGER-modified MMP-sensitive polyethylene glycol hydrogels induce chondrogenic differentiation of human mesenchymal stem cells

Tissue Eng Part A. 2014 Apr;20(7-8):1165-74. doi: 10.1089/ten.TEA.2013.0519. Epub 2014 Feb 10.

Abstract

The cellular microenvironment plays a crucial role in directing proliferation and differentiation of stem cells. Cells interact with their microenvironment via integrins that recognize certain peptide sequences of extracellular matrix proteins. This receptor-ligand binding has profound impact on cell fate. Interactions of human bone marrow mesenchymal stem cells (hMSCs) with the triple helical collagen mimetic, GPC(GPP)5-GFOGER-(GPP)5GPC-NH2, and the fibronectin adhesion peptide, RGD, were studied in degradable or nondegradable polyethylene glycol (PEG) gels formed by Michael-type addition chemistry. Proliferation, cytoskeletal morphology, and chondrogenic differentiation of encapsulated hMSCs were evaluated. The hMSCs adopted a highly spread morphology within the GFOGER-modified gels, whereas RGD induced a star-like spreading of the cells. hMSCs within GFOGER-modified degradable gels had a high proliferation rate compared with cells in peptide-free gels (p=0.017). Gene expression of type II collagen was highest in GFOGER-modified degradable gels after 21 days. Peptide incorporation increased GAG production in degradable gels after 7 and 21 days and GFOGER-modified degradable hydrogels had on average the highest GAG content, a finding that was confirmed by Alcian blue staining. In conclusion, the GFOGER peptide enhances proliferation in degradable PEG gels and provides a better chondrogenic microenvironment compared with the RGD peptide.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aggrecans / genetics
  • Aggrecans / metabolism
  • Amino Acid Sequence
  • Cell Differentiation / drug effects*
  • Cell Proliferation / drug effects
  • Cell Shape / drug effects
  • Cells, Cultured
  • Chondrogenesis / drug effects*
  • Collagen / chemistry
  • Collagen / pharmacology*
  • Collagen Type II / genetics
  • Collagen Type II / metabolism
  • Compressive Strength / drug effects
  • DNA / metabolism
  • Gene Expression Regulation / drug effects
  • Glycosaminoglycans / metabolism
  • Humans
  • Hydrogels / pharmacology*
  • Matrix Metalloproteinases / metabolism*
  • Mesenchymal Stem Cells / cytology*
  • Mesenchymal Stem Cells / drug effects
  • Mesenchymal Stem Cells / metabolism
  • Molecular Sequence Data
  • Oligopeptides / pharmacology
  • Peptide Fragments / chemistry
  • Peptide Fragments / pharmacology*
  • Peptides / chemistry
  • Peptides / pharmacology*
  • Polyethylene Glycols / pharmacology*
  • Staining and Labeling

Substances

  • Aggrecans
  • Collagen Type II
  • Glycosaminoglycans
  • Hydrogels
  • Oligopeptides
  • Peptide Fragments
  • Peptides
  • Polyethylene Glycols
  • arginyl-glycyl-aspartic acid
  • Collagen
  • DNA
  • Matrix Metalloproteinases