Computation models simulating notochordal cell extinction during early ageing of an intervertebral disc.
ABSTRACT Lower back pain due to intervertebral disc (IVD) degeneration is a prevalent problem which drastically affects the quality of life of millions of sufferers. Healthy IVDs begin with high populations of notochordal cells in the nucleus pulposus, while by the second stage of degeneration, these cells will be replaced by chondrocyte-like cells. Because the IVD is avascular, these cells rely on passive diffusion of nutrients to survive. It is thought that this transition in cell phenotype causes the shift of the IVD's physical properties, which impede the flow of nutrients. Our computational model of the IVD illustrates its ability to simulate the evolving chemical and mechanical environments occurring during the early ageing process. We demonstrate that, due to the insufficient nutrient supply and accompanying changes in physical properties of the IVD, there was a resultant exponential decay in the number of notochordal cells over time.
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ABSTRACT: An understanding of the processes that occur during development of the intervertebral disk can help inform therapeutic strategies for discogenic pain. This article reviews the literature to identify candidates that are found in or derived from the notochord or notochordal cells and evaluates the theory that such factors could be isolated and used as biologics to target the structural disruption, inflammation, and neurovascular ingrowth often associated with discogenic back pain. A systematic review using PubMed was performed with a primary search using keywords "(notochordal OR notochord) And (nerves OR blood vessels OR SHH OR chondroitin sulfate OR notch OR CTGF) NOT chordoma." Secondary searches involved keywords associated with the intervertebral disk and pain. Several potential therapeutic candidates from the notochord and their possible targets were identified. Studies are needed to further identify candidates, explore mechanisms for effect, and to validate the theory that these candidates can promote structural restoration and limit or inhibit neurovascular ingrowth using in vivo studies.06/2013; 3(3):201-218. DOI:10.1055/s-0033-1350053
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ABSTRACT: We extend a physiologically-based lattice model for the transport and metabolism of drugs in the liver lobule (liver functional unit) to consider structural and spatial variability. We compare predicted drug concentration levels observed exiting the lobule with their detailed distribution inside the lobule, and indicate the role that structural variation has on these results. Liver zonation and its role on drug metabolism represent another aspect of structural inhomogeneity that we consider here. Since various liver diseases can be thought to produce such structural variations, our analysis gives insight into the role of disease on liver function and performance. These conclusions are based on the dominant role of convection in well-vascularized tissue with a given structure.Theoretical Biology and Medical Modelling 09/2013; 10(1):53. DOI:10.1186/1742-4682-10-53 · 1.27 Impact Factor
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ABSTRACT: We develop a physiologically-based lattice model for the transport and metabolism of drugs in the called the lobule. In contrast to earlier studies, we have emphasized the dominant role of convection in well-vascularized tissue with a given structure. Estimates of convective, diffusive and reaction contributions are given. We have compared drug concentration levels observed exiting the lobule with their predicted detailed distribution inside the lobule, assuming that most often the former is accessible information while the latter is not.Theoretical Biology and Medical Modelling 09/2013; 10(1):52. DOI:10.1186/1742-4682-10-52 · 1.27 Impact Factor