Analysis of cell viability in intervertebral disc: Effect of endplate permeability on cell population.

Responsible for making and maintaining the extracellular matrix, the cells of intervertebral discs are supplied with essential nutrients by diffusion from the blood supply through mainly the cartilaginous endplates (CEPs) and disc tissue. Decrease in transport rate and increase in cellular activity may adversely disturb the intricate supply-demand balance leading ultimately to cell death and disc degeneration. The present numerical study aimed to introduce for the first time cell viability criteria into nonlinear coupled nutrition transport equations thereby evaluating the dynamic nutritional processes governing viable cell population and concentrations of oxygen, glucose and lactic acid in the disc as CEP exchange area dropped from a fully permeable condition to an almost impermeable one. A uniaxial model of an in vitro cell culture analogue of the disc is first employed to examine and validate cell viability criteria. An axisymmetric model of the disc with four distinct regions was subsequently used to investigate the survival of cells at different CEP exchange areas. In agreement with measurements, predictions of the diffusion chamber model demonstrated substantial cell death as essential nutrient concentrations fell to levels too low to support cells. Cells died away from the nutrient supply and at higher cell densities. In the disc model, the nucleus region being farthest away from supply sources was most affected; cell death initiated first as CEP exchange area dropped below approximately 40% and continued exponentially thereafter to depletion as CEP calcified further. In cases with loss of endplate permeability and/or disruptions therein, as well as changes in geometry and fall in diffusivity associated with fluid outflow, the nutrient concentrations could fall to levels inadequate to maintain cellular activity or viability, resulting in cell death and disc degeneration.

[1]  S. Rajasekaran,et al.  ISSLS Prize Winner: A Study of Diffusion in Human Lumbar Discs: A Serial Magnetic Resonance Imaging Study Documenting the Influence of the Endplate on Diffusion in Normal and Degenerate Discs , 2004, Spine.

[2]  Jill P. G. Urban,et al.  The effect of extracellular pH on matrix turnover by cells of the bovine nucleus pulposus , 2003, European Spine Journal.

[3]  A. Freemont,et al.  Accelerated cellular senescence in degenerate intervertebral discs: a possible role in the pathogenesis of intervertebral disc degeneration , 2007, Arthritis research & therapy.

[4]  S. Roberts,et al.  The cartilage end‐plate and intervertebral disc in scoliosis: Calcification and other sequelae , 1993, Journal of orthopaedic research : official publication of the Orthopaedic Research Society.

[5]  N. Boos,et al.  The Course of Macroscopic Degeneration in the Human Lumbar Intervertebral Disc , 2006, Spine.

[6]  R. Cailliet,et al.  Vertebral End-Plate Changes With Aging of Human Vertebrae , 1982, Spine.

[7]  Ruth M Ripley,et al.  Metabolism of the Intervertebral Disc: Effects of Low Levels of Oxygen, Glucose, and pH on Rates of Energy Metabolism of Bovine Nucleus Pulposus Cells , 2005, Spine.

[8]  T. Shibata,et al.  Morphologic Differences of the Vascular Buds in the Vertebral Endplate: Scanning Electron Microscopic Study , 1996, Spine.

[9]  A Shirazi-Adl,et al.  Computation of coupled diffusion of oxygen, glucose and lactic acid in an intervertebral disc. , 2007, Journal of biomechanics.

[10]  D. Haschtmann,et al.  Vertebral endplate trauma induces disc cell apoptosis and promotes organ degeneration in vitro , 2008, European Spine Journal.

[11]  D. Kletsas,et al.  Senescence in human intervertebral discs , 2006, European Spine Journal.

[12]  J. Urban,et al.  The measurement of fixed charged density in the intervertebral disc , 1979 .

[13]  S Holm,et al.  Nutrition of the intervertebral disc: solute transport and metabolism. , 1981, Connective tissue research.

[14]  A. Maroudas,et al.  Diffusion of small solutes into the intervertebral disc: as in vivo study. , 1978, Biorheology.

[15]  S Holm,et al.  Nutrition of the intervertebral disk. An in vivo study of solute transport. , 1977, Clinical orthopaedics and related research.

[16]  H. Brodin Paths of nutrition in articular cartilage and intervertebral discs. , 1955, Acta orthopaedica Scandinavica.

[17]  J. Urban,et al.  Nutrition of the Intervertebral Disc , 2004, Spine.

[18]  W. Gu,et al.  Effects of mechanical compression on metabolism and distribution of oxygen and lactate in intervertebral disc. , 2008, Journal of biomechanics.

[19]  A. Shirazi-Adl,et al.  Investigation of solute concentrations in a 3D model of intervertebral disc , 2009, European Spine Journal.

[20]  S. Bibby,et al.  Effect of nutrient deprivation on the viability of intervertebral disc cells , 2004, European Spine Journal.

[21]  S. Holm,et al.  Factors Influencing Oxygen Concentration Gradients in the Intervertebral Disc: A Theoretical Analysis , 1991, Spine.

[22]  A. Nachemson,et al.  In vitro diffusion of dye through the end-plates and the annulus fibrosus of human lumbar inter-vertebral discs. , 1970, Acta orthopaedica Scandinavica.

[23]  S. Rajasekaran,et al.  Pharmacological enhancement of disc diffusion and differentiation of healthy, ageing and degenerated discs , 2008, European Spine Journal.

[24]  B. Peng,et al.  The relationship between cartilage end-plate calcification and disc degeneration: an experimental study. , 2001, Chinese medical journal.

[25]  S. A. Shirazi-Adl,et al.  Nutrient supply and intervertebral disc metabolism. , 2006, The Journal of bone and joint surgery. American volume.

[26]  H. Horner,et al.  2001 Volvo Award Winner in Basic Science Studies: Effect of Nutrient Supply on the Viability of Cells From the Nucleus Pulposus of the Intervertebral Disc , 2001, Spine.

[27]  Keita Ito,et al.  2004 Young Investigator Award Winner: Vertebral Endplate Marrow Contact Channel Occlusions and Intervertebral Disc Degeneration , 2005, Spine.

[28]  A Shirazi-Adl,et al.  On the fibre composite material models of disc annulus--comparison of predicted stresses. , 1989, Journal of biomechanics.

[29]  J C Fairbank,et al.  Electrochemical Measurement of Transport Into Scoliotic Intervertebral Discs In Vivo Using Nitrous Oxide as a Tracer , 2001, Spine.

[30]  S. Bibby,et al.  Cell Viability in Scoliotic Discs in Relation to Disc Deformity and Nutrient Levels , 2002, Spine.

[31]  J. Urban,et al.  Evidence for a negative Pasteur effect in articular cartilage. , 1997, The Biochemical journal.

[32]  Keita Ito,et al.  Fluid flow and convective transport of solutes within the intervertebral disc. , 2004, Journal of biomechanics.

[33]  S. Roberts,et al.  Human Intervertebral Disc Aggrecan Inhibits Endothelial Cell Adhesion and Cell Migration In Vitro , 2005, Spine.

[34]  A. Nachemson,et al.  Correlation between lactate levels and pH in discs of patients with lumbar rhizopathies , 1968, Experientia.

[35]  A Shirazi-Adl,et al.  Finite Element Study of Nutrient Diffusion in the Human Intervertebral Disc , 2003, Spine.

[36]  V. Haughton,et al.  Measuring diffusion of solutes into intervertebral disks with MR imaging and paramagnetic contrast medium. , 1998, AJNR. American journal of neuroradiology.

[37]  A R Hargens,et al.  Intervertebral disc nutrition. Diffusion versus convection. , 1986, Clinical orthopaedics and related research.

[38]  A. Nachemson,et al.  Factors involved in the nutrition of the human lumbar intervertebral disc: cellularity and diffusion of glucose in vitro. , 1975, Journal of anatomy.

[39]  P. Farrell,et al.  Estimation of the permeability of cellulosic membranes from solute dimensions and diffusivities. , 1973, Journal of biomedical materials research.

[40]  S. Roberts,et al.  Biochemical and Structural Properties of the Cartilage End-Plate and its Relation to the Intervertebral Disc , 1989, Spine.

[41]  Penny Gowland,et al.  Prize Winner : What Influence Does Sustained Mechanical Load Have on Diffusion in the Human Intervertebral Disc ? An In Vivo Study Using Serial Postcontrast Magnetic Resonance Imaging , 2009 .

[42]  Thijs Grünhagen,et al.  Notochordal intervertebral disc cells: sensitivity to nutrient deprivation. , 2009, Arthritis and rheumatism.

[43]  V. Duance,et al.  Biology of the Intervertebral Disc , 2002 .

[44]  S Holm,et al.  Nutrition of the intervertebral disc: effect of fluid flow on solute transport. , 1982, Clinical orthopaedics and related research.

[45]  S. Roberts,et al.  Transport Properties of the Human Cartilage Endplate in Relation to Its Composition and Calcification , 1996, Spine.

[46]  F. Vittur,et al.  Degenerative Changes of Porcine Intervertebral Disc Induced by Vertebral Endplate Injuries , 2005, Spine.

[47]  S. Ullberg,et al.  Uptake of S35 in the intervertebral discs after injection of S35-sulphate. An autoradiographic study. , 1960, Acta orthopaedica Scandinavica.

[48]  A Shirazi-Adl,et al.  Analysis of nonlinear coupled diffusion of oxygen and lactic acid in intervertebral discs. , 2005, Journal of biomechanical engineering.