Use of FGF-2 and FGF-18 to direct bone marrow stromal stem cells to chondrogenic and osteogenic lineages

Abstract

Aim: Intervertebral disc degeneration/low back pain is the number one global musculoskeletal condition in terms of disability and socioeconomic impact. Materials & methods Multipotent mesenchymal stem cells (MSCs) were cultured in micromass pellets ± FGF-2 or -18 up to 41 days, matrix components were immunolocalized and gene expression monitored by quantitative-reverse transcription PCR. Results: Chondrogenesis occurred earlier in FGF-18 than FGF-2 cultures. Lower COL2A1, COL10A1 and ACAN expression by day 41 indicated a downregulation in chondrocyte hypertrophy. MEF2c, ALPL, were upregulated; calcium, decorin and biglycan, and 4C3 and 7D4 chondroitin sulphate sulfation motifs were evident in FGF-18 but not FGF-2 pellets. Conclusion: FGF-2 and -18 preconditioned MSCs produced cell lineages which promoted chondrogenesis and osteogenesis and may be useful in the production of MSC lineages suitable for repair of cartilaginous tissue defects. Lay abstract Intervertebral disc degeneration and low back pain is the number one global musculoskeletal disorder effecting 80% of the general population. A remedy for this condition is being eagerly sought as part of a WHO research priority. Stem cells are one potential therapy that shows promise in animal models, laboratory studies, and preclinical and early clinical trials. Conditioning of stem cells in the laboratory before injection may improve their efficacy for the alleviation of low back pain. In the present study we have developed a means of improving how stem cells form cartilage and bone, which should be of application in the repair of spinal defects.