title: Analysis of cell viability in intervertebral disc: Effect of endplate permeability on cell population.
abstract: 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.
authors.affiliation: Department of Mechanical Engineering, Ecole Polytechnique, P.O. Box 6079, Station 'centre-ville', Montreal, Quebec, Canada H3C 3A7. abshir@meca.polymtl.ca
authors.forename: A
authors.initials: A
authors.lastname: Shirazi-Adl
authors.forename: M
authors.initials: M
authors.lastname: Taheri
authors.forename: J P G
authors.initials: JP
authors.lastname: Urban
mesh_terms: D000818:Animals; D001692:Biological Transport; D002417:Cattle; D016923:Cell Death; D002470:Cell Survival; D005947:Glucose / Q000378:metabolism*; D007403:Intervertebral Disc / Q000378:metabolism* / Q000473:pathology; D019344:Lactic Acid / Q000378:metabolism*; D008954:Models, Biological; D010100:Oxygen / Q000378:metabolism*; D010539:Permeability; D046509:Tissue Culture Techniques
chemical_list: D019344:Lactic Acid; D005947:Glucose; D010100:Oxygen