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Project ID: QLK6-CT-2002-02582
Finanziato nell'ambito di: FP5-LIFE QUALITY
Paese: United Kingdom

Human intervertebral disc cells promote nerve growth over substrata of human intervertebral disc aggrecan

Study Design.
Co-culture assays of the migration and interaction of human intervertebral disc (IVD) cells and chick sensory nerves on alternate substrata of collagen and aggrecan.

To examine the effects of aggrecan on disc cell migration, how disc cells and sensory nerves interact, and whether previously reported inhibitory effects of aggrecan on sensory nerve growth are affected by disc cells.

Summary of Background Data.
Human IVD aggrecan is inhibitory to sensory nerve growth in vitro, suggesting that a loss of aggrecan from the disc may have a role to play in the increased innervation seen in disc degeneration. Endothelial cells that appear to co-migrate with nerves into degenerated IVD express neurotrophic factors, but the effects of disc cells on nerve growth are not known.

Human disc cells were seeded onto tissue culture plates that had been coated with type I collagen and human IVD aggrecan. Explants of chick dorsal root ganglia (DRG) were subsequently added to the plates and sensory neurite outgrowth stimulated by the addition of nerve growth factor (NGF). The migration and interaction of the disc cells and sensory neurites, in the context of the different matrix substrata, were examined by time-lapse video and fluorescence microscopy. The effects of disc cell conditioned medium on nerve growth were also examined.

Disc cells spread and migrated on collagen until they encountered the aggrecan substrata, where some cells but not all were repelled. In co-culture, DRG neurites extended onto the collagen / disc cells until they encountered the aggrecan where, like the disc cells, many were repelled. However, in the presence of disc cells, some neurites were able to cross onto this normally inhibitory substratum. The number of neurite crossings onto aggrecan correlated significantly with the number of disc cells present on the aggrecan. In control experiments using DRG alone, all extending neurites were repelled at the collagen / aggrecan border. Conditioned medium from disc cell cultures stimulated DRG neurite outgrowth on collagen, but did not increase neurite crossing onto aggrecan substrata.

Human disc cells migrate across aggrecan substrata that are repellent to sensory DRG neurites. Disc cells synthesise neurotrophic factors in vitro that promote neurite outgrowth. Furthermore, the presence of disc cells in co-culture with DRG partially abrogates the inhibitory effects of aggrecan on nerve growth. These findings have important implications for the regulation of nerve growth into the intervertebral disc, but whether disc cells promote nerve growth in vivo remains to be determined.


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