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

Harmonization and standardization of nucleus pulposus cell extraction and culture methods

Background In vitro studies using nucleus pulposus (NP) cells are commonly used to investigate disc cell biology and pathogenesis, or to aid in the development of new therapies. However, lab-to-lab variability jeopardizes the much-needed progress in the field. Here, an international group of spine scientists collaborated to standardize extraction and expansion techniques for NP cells to reduce variability, improve comparability between labs and improve utilization of funding and resources. Methods The most commonly applied methods for NP cell extraction, expansion, and re-differentiation were identified using a questionnaire to research groups worldwide. NP cell extraction methods from rat, rabbit, pig, dog, cow, and human NP tissue were experimentally assessed. Expansion and re-differentiation media and techniques were also investigated. Results Recommended protocols are provided for extraction, expansion, and re-differentiation of NP cells from common species utilized for NP cell culture. Conclusions This international, multilab and multispecies study identified cell extraction methods for greater cell yield and fewer gene expression changes by applying species-specific pronase usage, 60–100 U/ml collagenase for shorter durations. Recommendations for NP cell expansion, passage number, and many factors driving successful cell culture in different species are also addressed to support harmonization, rigor, and cross-lab comparisons on NP cells worldwide

MOLECULAR PHENOTYPING OF PATIENT CHONDROCYTES REVEALS GENES AND PATHWAYS INVOLVED IN OSTEOARTHRITIS

Molecular Epidemiolog

Predicting effect of changes in ‘fishable’ areas on fish and fisheries

This report aims to investigate the available tools for predicting the impact of various spatial management options on fisheries distribution, yield, profitability, and selectivity. Such spatial plans may affect the remaining ‘fishable’ areas by displacing and concentrating the fishing pressure, and so may alter stock abundances, distributions, size- and species catch composition and fuel expenditure and cost. The report provides early insights into how spatial plans that exclude certain fishing activities may affect these outcomes. Spatially explicit approaches are used, along with scenarios of underlying stock productivities and distributions, to assess the performance of spatial management measures. Scenario-based testing is conducted to examine the interrelated effects of management options and stock productivity. A major aspect of the work involved gathering and organizing information on specific zones from several sources such as Natura2000, CDDA, SPA, SAC, and UK-defined areas. We found that most of these zones did not have any previous management plans in place that would outline fishing restrictions. Therefore, we developed a method of assigning limitations to certain fishing techniques based on the perceived vulnerability of specific areas to these practices. This approach has allowed for an examination of how these restrictions potentially affect fish and fisheries.Initially, we used a static approach in anticipating the potential fishing effort displacement to measure the impact of fishing in the Northeast Atlantic area. Our research shows that while such spatial management measures may reduce fishing opportunities, it may be possible to offset in the short term some of these spatial opportunity losses by fishing in nearby locations (Figure 1). On the Med side, an analysis of fishing effort displacement from restricted areas in the Adriatic Sea is exemplified in a before/after situation, showing that the effort is not reduced but redistributed and can further redistribute far from the restricted areas.If in the short term, spatial management may increase operating costs by displacing the effort, this may eventually be recovered in the long term if the stock is recovering from previous overfishing. To determine whether conservation measures (such as Marine Protected Areas) that limit specific fishing techniques and areas could help mitigate the negative effects of fishing, a more advanced approach to fisheries management is required. This involves using a dynamic approach deploying spatial bioeconomic models that consider changes in environmental drivers and spatial restrictions, allowing it to assess potential changes in fishing effort facing, for example, new regulatory or ecological conditions. While bioeconomic models require more data and assumptions to forecast "alternative futures", they offer a more comprehensive approach to fisheries management, which is particularly useful as testing MPAs effects in real life is a challenge. A suite of bioeconomic models has been deployed to provide preliminary findings about the effect of spatial restrictions on fish, fisheries, benthos and bycatch:•International fisheries active in the North Sea were modeled using DISPLACE, testing the implementation of spatial restrictions to specific fishing techniques. Based on the simulations, the benthos status improved in areas where bottom fishing was excluded from previously fished areas and decreased in newly fished areas. However, the gain by EU closure areas was limited and no change in fish size selectivity detected as these areas are not really significant for bottom fishing and have not been initially designated to modify selectivity.•In the eastern Ionian Sea, different spatial restrictions for fishing techniques were evaluated using the DISPLACE model. While there may have been advantages to the fishing restrictions, there has been an increase in both unwanted catch and fishing effort, and no significant improvements were observed in the harvesting of adult fish. The alternative scenarios tested were insufficient to make fishing fleets more selective. Additionally, certain fishing fleets were economically adversely affected.•East Adriatic trawlers may benefit from being forced closer to shore after the closure of their traditional fishing grounds while the Italian trawling fleet experiences higher steaming costs, likely due to the closure of nursery grounds and FRAs and redistribution to other areas. ECOSPACE predicted that the mean trophic level of fish caught in deeper waters, closed to bottom trawlers but still accessible to pelagic fisheries, will increase. ECOSPACE indicated a marked rise in biodiversity in the central Adriatic area under the closures scenario. The reported outcome for ECOSPACE should be considered preliminary as it may have been influenced by the assumptions used to build and parameterize the model.•ECOSPACE predicted a significant rise in biomass for the southern North Sea in response to area closures. Fish biomass could increase by up to 15%. However, this increase may not be sufficient to compensate for the decline in biomass outside the MPA from more pressure on specific fish species. This, in turn, caused a decrease in overall catches. Within the MPAs, all fishing fleets experienced losses of up to 50%, while outside the MPAs, there was an increase of up to 13% in catches. Nonetheless, the gains outside the MPAs did not compensate for the losses incurred due to the closures.•ECOSPACE investigation on how spatial fisheries management affects the food web and fisheries in the eastern Ionian Sea was used to evaluate the spatial distribution of fishing effort for two scenarios - one with existing closed areas and another with possible future closed areas. Preliminary findings indicate that if all fishing activities are restricted from MPAs (as in the second scenario), there is an increase in fishing effort throughout the study area, rather than just around the MPAs.•Using an agent-based model of the southern North Sea and the German fisheries, spatial restrictions were shown to possibly result in reduction in fishing effort, concentration of fishing effort in the remaining open areas, longer steaming times, and lower profits. The spatial scenarios heavily affect the German shrimp fishery due to large overlaps with coastal shrimp fishing grounds, while flatfish and Nephrops fisheries are less affected. Scenarios reduced the fishing effort of all métiers suggesting that switching métiers and relocating fishing effort could not negate the impact of spatial fishing closures.•In the North Sea, the OSMOSE model was used to test scenarios of effort redistribution and effort reduction. The results indicated a slight increase in the biomass of demersal species, but a significant decrease in the biomass of pelagic species. Both scenarios showed an increase in the relative biomass of protected, endangered, and threatened (PET) species when effort was reduced. Additionally, changes in the food web led to an increase in the catch of commercial species above minimum conservation size.•A spatial BEMTOOL is being implemented applied to the Adriatic and western Ionian Seas active and passive demersal gears fleet segments. The effort data for the main ports in the study area was explored to identify the fishing grounds that are more frequently visited by fishers and to gain insights into their fishing strategies.In summary, prohibition of certain fishing techniques in all currently designated MPAs has minimal impact on the fisheries economy of most fleet-segments examined and fish populations in the short term. This is primarily because these areas are preserved due to their significance as hotspots of EU marine biodiversity, rather than selected for a high abundance of commercial fish. Some segments, however, may require >15% extra effort to break even. In an upcoming study, SEAwise partners will investigate conservation areas the selectivity of fish size