European Spine Journal

, Volume 20, Issue 6, pp 962–971

Differential response of human bone marrow stromal cells to either TGF-β1 or rhGDF-5

  • Benjamin Gantenbein-Ritter
  • Lorin M. Benneker
  • Mauro Alini
  • Sibylle Grad
Original Article

DOI: 10.1007/s00586-010-1619-z

Cite this article as:
Gantenbein-Ritter, B., Benneker, L.M., Alini, M. et al. Eur Spine J (2011) 20: 962. doi:10.1007/s00586-010-1619-z

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.

Keywords

Coculture Bone marrow stromal cells Growth factor rhGDF-5 CDMP-1 Bovine nucleus pulposus cells Gene expression Differentiation 

Copyright information

© Springer-Verlag 2010

Authors and Affiliations

  • Benjamin Gantenbein-Ritter
    • 1
    • 2
  • Lorin M. Benneker
    • 3
  • Mauro Alini
    • 1
  • Sibylle Grad
    • 1
  1. 1.AO Research Institute DavosDavosSwitzerland
  2. 2.ARTORG Center, Spine Research CenterUniversity of BernBernSwitzerland
  3. 3.Insel University HospitalBernSwitzerland