Chondrogenic differentiation of human embryonic stem cell-derived cells in arginine-glycine-aspartate-modified hydrogels

Tissue Eng. 2006 Sep;12(9):2695-706. doi: 10.1089/ten.2006.12.2695.

Abstract

Human embryonic stem cells (hESCs) have the potential to self-renew and generate multiple cell types, producing critical building blocks for tissue engineering and regenerative medicine applications. Here, we describe the efficient derivation and chondrogenic differentiation of mesenchymal-like cells from hESCs. These cells exhibit mesenchymal stem cell (MSC) surface markers, including CD29, CD44, CD105, and platelet-derived growth factor receptor-alpha. Under appropriate growth conditions, the hESC-derived cells proliferated without phenotypic changes and maintained MSC surface markers. The chondrogenic capacity of the cells was studied in pellet culture and after encapsulation in poly(ethylene glycol)-diacrylate (PEGDA) hydrogels with exogenous extracellular proteins or arginineglycine- aspartate (RGD)-modified PEGDA hydrogels. The hESC-derived cells exhibited growth factor- dependent matrix production in pellet culture but did not produce tissue characteristic of cartilage morphology. In PEGDA hydrogels containing exogenous hyaluronic acid or type I collagen, no significant cell growth or matrix production was observed. In contrast, when these cells were encapsulated in RGDmodified poly(ethylene glycol)hydrogels, neocartilage with basophilic extracellular matrix deposition was observed within 3 weeks of culture, producing cartilage-specific gene up-regulation and extracellular matrix production. Our results indicate that precursor cells characteristic of a MSC population can be cultured from differentiating hESCs through embryoid bodies, thus holding great promise for a potentially unlimited source of cells for cartilage tissue engineering.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acids / chemistry
  • Antigens, Differentiation / biosynthesis
  • Cell Culture Techniques
  • Cell Differentiation / physiology*
  • Cells, Cultured
  • Cells, Immobilized / cytology
  • Cells, Immobilized / physiology
  • Chondrogenesis / physiology*
  • Embryo, Mammalian / cytology
  • Embryo, Mammalian / physiology*
  • Extracellular Matrix / metabolism
  • Humans
  • Hydrogels* / chemistry
  • Mesenchymal Stem Cells / cytology
  • Mesenchymal Stem Cells / physiology*
  • Oligopeptides* / chemistry
  • Polyethylene Glycols* / chemistry
  • Tissue Engineering / methods

Substances

  • Amino Acids
  • Antigens, Differentiation
  • Hydrogels
  • Oligopeptides
  • poly(ethylene glycol)diacrylate
  • Polyethylene Glycols