Differential response of human bone marrow stromal cells to either TGF-β(1) or rhGDF-5

Eur Spine J. 2011 Jun;20(6):962-71. doi: 10.1007/s00586-010-1619-z. Epub 2010 Nov 18.

Abstract

Cell therapy along with growth factor injection is currently widely investigated to restore the intervertebral disc. However, there is increasing evidence that transplanted unconditioned bone marrow-derived stromal cells (BMSCs) cannot thrive in the intervertebral disc "niche". Moreover, uncertainty exists with respect to the cell phenotype that would be suitable to inject. The intervertebral disc cell phenotype only recently has been started to be characterised using transcriptomics profiling. Recent findings suggest that cytokeratin 19 (KRT-19) could be used as a potential candidate marker for the intervertebral disc, or more specifically the nucleus pulposus cell (NPC) phenotype. We present in vitro cell culture data using alginate bead culture of primary human BMSCs exposed to the standard chondrogenic stimulus, transforming growth factor beta-1 (TGF-β), the growth and differentiation factor 5 and/or bovine NPCs to induce a potential "discogenic" pathway. Chondrogenic induction via TGF-β pathway provoked down-regulation of KRT-19 gene expression in four out of five donors after 18 days of culture, whereas KRT-19 expression remained unchanged in the "discogenic" groups. In addition, the ratio of aggrecan/collagen II gene expression showed a remarkable difference (of at least 3 magnitudes) between the chondrogenic stimulus (low ratio) and the discogenic stimulus (high ratio). Therefore, KRT-19 and aggrecan/collagen II ratio may be potential markers to distinguish chondrogenic from "discogenic" differentiation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aggrecans / genetics
  • Aggrecans / metabolism
  • Bone Marrow Cells / cytology
  • Bone Marrow Cells / drug effects*
  • Bone Marrow Cells / metabolism
  • Cells, Cultured
  • Female
  • Growth Differentiation Factor 5 / metabolism
  • Growth Differentiation Factor 5 / pharmacology*
  • Humans
  • Intervertebral Disc / cytology
  • Intervertebral Disc / drug effects
  • Intervertebral Disc / metabolism
  • Keratin-19 / genetics
  • Keratin-19 / metabolism
  • Male
  • Middle Aged
  • Recombinant Proteins / metabolism
  • Recombinant Proteins / pharmacology*
  • Stromal Cells / cytology
  • Stromal Cells / drug effects*
  • Stromal Cells / metabolism
  • Transforming Growth Factor beta1 / metabolism
  • Transforming Growth Factor beta1 / pharmacology*

Substances

  • ACAN protein, human
  • Aggrecans
  • Growth Differentiation Factor 5
  • Keratin-19
  • Recombinant Proteins
  • Transforming Growth Factor beta1