Growth factors for sequential cellular de- and re-differentiation in tissue engineering

Biochem Biophys Res Commun. 2002 May 31;294(1):149-54. doi: 10.1016/S0006-291X(02)00439-4.

Abstract

A model system for the in vitro generation of cartilaginous constructs was used to study a tissue engineering paradigm whereby sequentially applied growth factors promoted chondrocytes to first de-differentiate into a proliferative state and then re-differentiate and undergo chondrogenesis. Early cultivation in medium with supplemental TGF-beta1/FGF-2 doubled cell fractions in 2-week constructs compared to unsupplemented controls. Subsequent culture with supplemental IGF-I yielded large 4-week constructs with high fractions of cartilaginous extracellular matrix (ECM) and high compressive moduli, whereas prolonged culture with supplemental FGF-2 yielded small 4-week constructs with low ECM fractions and moduli. Sequential supplementation with TGF-beta1/FGF-2 and then IGF-I yielded 4-week constructs with type-specific mRNA expression and protein levels that were high for type II and negligible for type I collagen, in contrast to other growth factor regimens studied. The data demonstrate that structural, functional, and molecular properties of engineered cartilage can be modulated by sequential application of growth factors.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Cartilage / cytology*
  • Cartilage / drug effects
  • Cattle
  • Cell Differentiation / drug effects
  • Cells, Cultured
  • Chondrocytes / cytology
  • Chondrocytes / drug effects*
  • Culture Media
  • Extracellular Matrix / metabolism
  • Fibroblast Growth Factor 2 / administration & dosage
  • Fibroblast Growth Factor 2 / pharmacology*
  • Insulin-Like Growth Factor I / administration & dosage
  • Insulin-Like Growth Factor I / pharmacology*
  • RNA, Messenger / metabolism
  • Structure-Activity Relationship
  • Tissue Engineering / methods*
  • Transforming Growth Factor beta / administration & dosage
  • Transforming Growth Factor beta / pharmacology*
  • Transforming Growth Factor beta1

Substances

  • Culture Media
  • RNA, Messenger
  • Transforming Growth Factor beta
  • Transforming Growth Factor beta1
  • Fibroblast Growth Factor 2
  • Insulin-Like Growth Factor I