Abstract
Introduction: Intervertebral disc (IVD) cell transplantation is used to treat back pain. However, IVD cell activity may also contribute to pathology, e.g. IVD cells can undergo senescence or promote nerve growth, which in the IVD is associated with discogenic back pain. Serum deprivation of bovine IVD cells results in cell senescence. We have examined the influence of oxygen supply combined with serum deprivation on human IVD cells.
Methods: Cells from herniated IVD (n=3 patients) were subjected to serum deprivation and then cultured under hypoxic (1%) or atmospheric (21%) conditions for 10 days. IVD cell growth, viability and cell senescence (via Senescence Associated β-galactosidase activity; SA β-gal) were examined. The growth and migration of HMEC-1 (endothelial) and SH-SY5Y (neuronal) cells treated with conditioned medium from the IVD cell cultures (1% versus 21% oxygen) were subsequently monitored.
Results: Hypoxia significantly decreased IVD cell proliferation, but was also found to reduce cell senescence. Hence, the proportions of SA β-gal positive IVD cells in 1% and 21% oxygen at day 10 were 18±6% and 56±10%, respectively. There was no marked difference in cell viability (> 95%). Conditioned medium from IVD cells cultured under hypoxia stimulated endothelial and neural cell growth (determined via the MTS assay) and endothelial cell migration and neurite outgrowth to an extent that was significantly greater than conditioned medium from IVD cells cultured at 21% oxygen.
Conclusions: The trophic activity of human IVD cells is responsive to oxygen supply. However, hypoxia may influence the capacity of IVD cells to reduce back pain for better or worse.
Conflicts of Interest: None
Source of Funding: Institute of Orthopaedics, RJAH Orthopaedic Hospital.
Correspondence should be addressed to: SBPR at the Royal College of Surgeons, 35–43 Lincoln’s Inn Fields, London WC2A 3PE, England.
