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Title: The effect of shear stress on bovine nucleus pulposus cells
Author: Wilson, Cate
ISNI:       0000 0004 8505 930X
Awarding Body: Newcastle University
Current Institution: University of Newcastle upon Tyne
Date of Award: 2019
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Low back pain affects most people at some point in their lives, and intervertebral disc degeneration is a common cause of this pain. The nucleus pulposus is the first structure to fail in intervertebral disc degeneration. Gaining a greater understanding of the nucleus pulposus cell and its response to mechanical stimuli may be useful in tailoring the next cell-based regenerative therapy and preventative therapies. The nucleus pulposus is a highly hydrated, porous tissue and changes in spinal loading create fluid movement throughout the tissue, which causes fluid shear stress on the tissue and cells. This research has investigated shear stress rates of 0.1, 1.0 and 4.0 dyne/cm2 on bovine nucleus pulposus cells. Steady and pulsed flow were studied over 1, 4, 8 and 24 hours using Ibidi VI0.4 chambers. Results showed shear stress affects the morphology and gene expression of bovine nucleus pulposus cells. Morphological changes associated with cell detachment and reduced proliferation were seen in cells exposed to 1.0 dyne/cm for 4 and 8 hours and 4.0 dyne/cm2 for 1, 4 and 8 hours. After 24 hours in 1.0 dyne/cm2 and 4.0 dyne/cm2 all cells had detached from the Ibidi VI0.4 slides. There was an increase in cell proliferation in cells exposed to 0.1 dyne/cm2 for 4 hours in steady flow and no change in cell number compared to control at 1, 8 and 24 hours in steady and pulsed flow. Changes in gene expression in 4.0 dyne/cm2 flow were consistent with changes associated with catabolic metabolism; downregulation of collagen 2 and aggrecan and upregulation of aggrecanase 1 and 2. Results comparing steady and pulsed flow and gene expression changes at 0.1 and 1.0 dyne/cm2 were inconclusive, further studies with a larger sample size could help to clarify these effects. These findings are important in guiding researchers in the development of optimal perfusion bioreactor conditions for cell-seeded nucleus pulposus regeneration therapies. The implications for research to increase our understanding of fluid flow through the intervertebral disc during exercise as a preventative measure for disc degeneration are also discussed.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available