Current strategies for treatment of intervertebral disc degeneration: substitution and regeneration possibilities

Background: Intervertebral disc degeneration has an annual worldwide socioeconomic impact masked as low back pain of over 70 billion euros. This disease has a high prevalence over the working age class, which raises the socioeconomic impact over the years. Acute physical trauma or prolonged intervertebral disc mistreatment triggers a biochemical negative tendency of catabolic-anabolic balance that progress to a chronic degeneration disease. Current biomedical treatments are not only ineffective in the long-run, but can also cause degeneration to spread to adjacent intervertebral discs. Regenerative strategies are desperately needed in the clinics, such as: minimal invasive nucleus pulposus or annulus fibrosus treatments, total disc replacement, and cartilaginous endplates decalcification. Main Body: Herein, it is reviewed the state-of-the-art of intervertebral disc regeneration strategies from the perspective of cells, scaffolds, or constructs, including both popular and unique tissue engineering approaches. The premises for cell type and origin selection or even absence of cells is being explored. Choice of several raw materials and scaffold fabrication methods are evaluated. Extensive studies have been developed for fully regeneration of the annulus fibrosus and nucleus pulposus, together or separately, with a long set of different rationales already reported. Recent works show promising biomaterials and processing methods applied to intervertebral disc substitutive or regenerative strategies. Facing the abundance of studies presented in the literature aiming intervertebral disc regeneration it is interesting to observe how cartilaginous endplates have been extensively neglected, being this a major source of nutrients and water supply for the whole disc. Conclusion: Severalinnovative avenues for tackling intervertebral disc degeneration are being reported â from acellular to cellular approaches, but the cartilaginous endplates regeneration strategies remain unaddressed. Interestingly, patient-specific approaches show great promise in respecting patient anatomy and thus allow quicker translation to the clinics in the near future.The authors would like to acknowledge the support provided by the Portuguese Foundation for Science and Technology (FCT) through the project EPIDisc (UTAP-EXPL/BBBECT/0050/2014), funded in the Framework of the “International Collaboratory for Emerging Technologies, CoLab”, UT Austin|Portugal Program. The FCT distinctions attributed to J. Miguel Oliveira (IF/00423/2012 and IF/01285/ 2015) and J. Silva-Correia (IF/00115/2015) under the Investigator FCT program are also greatly acknowledged.info:eu-repo/semantics/publishedVersio

Loading-Induced Stress Response in the Intervertebral Disc

Conference theme: The Intervertebral Disc - from Degeneration to Therapeutic Motion PreservationThe abstract can be viewed at http://www.spineresearchforum.org/WFSR_2014_Thieme_AbstractBook_with_Cover.pdfIntroduction Previous research has been done to study the effect of mechanical loading on intervertebral disc (IVD) cells. However, few studies have investigated in whether the IVD cells perceive mechanical loading as stress and respond by expression of stress response proteins such as heat shock proteins (HSP). Studies have shown that stress response can be seen in cell line chondrocytes under hydrostatic pressure. On the other hand, studies have also shown that expression of heat shock protein-72 (HSP72) and HSP27was associated with disc degeneration and IVD cells can secrete HSP70 in response to oxidative stress. This study aims to study the stress response in the IVD in response to compressive loading and whether the disc cells are able to adapt to the loading. The outcome of the study will help to understand how the disc cells adapt or cope with mechanical stress. Materials and Methods Fresh adult bovine caudal discs were harvested and cultured with dynamic compressive loading applied at physiological range magnitude, 0.1 to 0.6 MPa. The culture condition was such that the discs underwent 2 hours of dynamic loading, followed by 22 hours of resting for 2 days. Samples were retrieved at different time points: right after loading (Dyna) and right after resting (DyNa+rest). Positive control discs were put under static loading (0.35 MPa, static) and heat shock (43° C, HS) exposed for 2 h/d during 2 days and gene expression was quantified right after the treatments. Both nucleus pulposus (NP) and annulus fibrosus (AF) were retrieved for gene expression study of the cellular stress response genes. HSP72 and heat shock factor-1 (HSF1). HSP72 is the general stress response protein which is upregulated in the cell in response to stress while HSF1 is the transcriptional factor of HSP72. The expression was normalized to free swelling control. Results In the NP of the bovine disc, both positive controls (HS and static) expressed high level of HSP72, confirming their expression in the NP tissues and their response to stress. For the experimental groups, the expression of HSP72 was upregulated after loading, decreased after resting but was again increased after second round of loading at day 2. On the other hand, HSF1 expression increased after resting in the day 1 loading and peaked at day 2 after loading. For the AF tissues, the expression of HSF1 was low in most of the groups including the positive control, even the HSP72 expression was high in these two groups. The expression of HSP72 in AF tissues was decreasing with both resting and an additional round of loading. The pattern of HSF1 expression of AF tissues was similar to the NP tissues where the expression was the highest 2 days after loading. Conclusion This study showed that the IVD cells do upregulate the stress response proteins expression in response to loading induced stress. The cells express HSP72 in response to the stress while HSF1 may have a slower and transient expression. The increase in HSP72 and HSF1 expression after two rounds of loading may indicate more cycles are needed to see whether there is adaptation in stress response induced by mechanical loading. Disclosure of Interest None declare

Cellular stress response of intervertebral cells under mechanical loading

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