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The Intervertebral Disc and Its Role in Spinal Disorders
intra-disc injection of these agents alone may not fulfil this prerequisite; degeneration and back pain (and therefore developing appropriate new
rather, the delivery of genes that encode the proteins or growth factors therapies) would be improved if better diagnosis were possible. ■
in question may be required to provide a prolonged stimulus. It has been
demonstrated that disc cells can be genetically modified in situ.
20
Acknowledgements
However, intervention using gene therapy approaches often raises ethical Simon Stephan and Audrey Gilson are supported by funding from the
concerns regarding induction of inflammatory responses, ectopic Biotechnology and Biological Sciences Research Council (BBRSC).
expression of the transgene, tumour formation or even inadvertently Jill Urban is supported by the Arthritis Research Council.
influencing germline gene expression.
Tissue Engineering Editor’s Recommendation
Tissue engineering is currently used clinically as a technique to repair ‘Rumours of my death may have been greatly
other cartilaginous tissues, for example articular cartilage,
21–23
and is exaggerated’: a brief review of cell death in
being employed in at least one centre for the intervertebral disc.
24
This human intervertebral disc disease and
is based on the hypothesis that implantation of cells into a damaged implications for cell transplantation therapy.
disc may boost its capacity to recover structure and function. Stem
Johnson WE, Roberts S, Biochem Soc Trans, 2007:35(Pt 4):680–82.
cells are possible candidates for this purpose since numerous studies
have indicated that they have the ability to differentiate into various The avascular nature of the human intervertebral disc is thought
cell types.
25,26
These can be sourced from various tissue types to reduce the ability of resident disc cells to maintain their
including adipose tissue
27
and bone marrow;
28,29
the cell population extracellular matrix, rendering the tissue susceptible to
can be expanded in vitro and then induced into a chondrogenic degeneration. It has also been suggested that the lack of a blood
phenotype
30
in appropriate culture conditions. However, it remains supply may result in disc cell death via nutrient deprivation.
uncertain whether the ‘induced’ cell is close enough to a disc cell to Therefore, transplanting new cells into the disc to promote tissue
offer regenerative potential for damaged discs, or even whether cells regeneration would be akin to ‘putting cells in a coffin’ and
introduced into damaged disc would remain alive and fully functional doomed to failure. This review considers the available evidence for
for significant periods of time. cell death in the human intervertebral disc, describing briefly the
methods used to assay such death, and concludes that further
Conclusions analysis is required to ascertain whether extensive cell death truly
It is clear that new approaches to combat disc degeneration and back is a marked feature of human intervertebral discs and whether it
pain are required by an increasingly aged population. Further advances bears any relationship to disc degeneration and, hence,
in gene therapy and/or tissue engineering may unveil potential new regenerative strategies. ■
therapies that will both alleviate low-back pain and restore spinal
function. However, progress in researching mechanisms of disc
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EUROPEAN MUSCULOSKELETAL REVIEW 45
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