Objective. The nucleus pulposus (NP) of the intervertebral disc develops from the notochord. Humans and other species in which notochordal cells (NCs) disappear to be replaced by chondrocyte-like mature NP cells (MNPCs) frequently develop disc degeneration, unlike other species that retain NCs. The reasons for NC disappearance are unknown. In humans, the change in cell phenotype (to MNPCs) coincides with changes that decrease nutrient supply to the avascular disc. We undertook this study to test the hypothesis that the consequent nutrient stress could be associated with NC disappearance.Methods. We measured cell densities and metabolic rates in 3-dimensional cultures of porcine NCs and bovine MNPCs, and we determined survival rates under conditions of nutrient deprivation. We used scanning electron microscopy to examine end plate porosity of discs with NCs and those with MNPCs. Nutrientmetabolite profiles and cell viability were calculated as a function of cell density and disc size in a consumption/ diffusion mathematical model.Results. NCs were more active metabolically and more susceptible to nutrient deprivation than were MNPCs. Hypoxia increased rates of glycolysis in NCs but not in MNPCs. Higher end plate porosity in discs with NCs suggested greater nutrient supply in keeping with higher nutritional demands. Mathematical simulations and experiments using an analog disc diffusion chamber indicated that a fall in nutrient concentrations resulting from increased diffusion distance during growth and/or a fall in blood supply through end plate changes could instigate NC disappearance.Conclusion. NCs demand more energy and are less resistant to nutritional stress than MNPCs, which may shed light on the fate of NCs in humans. This provides important information about prospective NC tissue engineering approaches.The intervertebral discs are cartilaginous structures interspersed between the vertebral bodies, providing flexibility to the spinal column. They consist of 3 regions: the outer annulus fibrosus (AF) surrounding the inner nucleus pulposus (NP) and a thin hyaline cartilaginous end plate lying between the disc and the adjacent vertebral bodies. The AF and NP differ in developmental origin, with the annulus arising from the mesenchyme and the nucleus from the notochord (1,2). During development the highly hydrated NP is populated by clusters of large vacuolated notochordal cells (NCs) of distinct molecular phenotype (2,3). In humans and some other species (e.g., cattle, chondrodystrophoid dogs) but not in others (e.g., rodents, pigs), NCs disappear before maturity to be replaced by chondrocyte-like cells of unknown provenance (here called mature NP cells [MNPCs]), which synthesize a more collagenous and less hydrated matrix (1,4-6).
The metabolic environment of disc cells is governed by the avascular nature of the tissue. Because cellular energy metabolism occurs mainly through glycolysis, the disc cells require glucose for survival and produce lactic acid at high rates. Oxygen is also necessary for cellular activity, although not for survival; its pathway of utilization is unclear. Because the tissues are avascular, disc cells depend on the blood supply at the margins of the discs for their nutrients. The nucleus and inner anulus of the disc are supplied by capillaries that arise in the vertebral bodies, penetrate the subchondral bone, and terminate at the bone-disc junction. Small molecules such as glucose and oxygen then reach the cells by diffusion under gradients established by the balance between the rate of transport through the tissue to the cells and the rate of cellular demand. Metabolites such as lactic acid are removed by the reverse pathway. The concentrations of nutrients farthest from the source of supply can thus be low; oxygen concentrations as low as 1% have been measured in the discs of healthy animals. Although gradients cannot be measured easily in humans, they can be calculated. Measured concentrations in surgical patients are in agreement with calculated values.
With this novel preparation and culturing technique, endplate permeability could be maintained, which allowed culturing of intact disc explants with endplates for up to 7 days.
Purpose To evaluate the feasibility of image fusion (IF) of preprocedural arterial-phase computed tomography with intraprocedural fluoroscopy for roadmapping in endovascular repair of complex aortic aneurysms, and to compare this approach versus current roadmapping methods (ie, two-dimensional [2D] and three-dimensional [3D] angiography). Materials and Methods Thirty-seven consecutive patients with complex aortic aneurysms treated with endovascular techniques were retrospectively reviewed; these included aneurysms of digestive and/or renal arteries and pararenal and juxtarenal aortic aneurysms. All interventions were performed with the same angiographic system. According to the availability of different roadmapping software, patients were successively placed into three intraprocedural image guidance groups: (i) 2D angiography (n = 9), (ii) 3D rotational angiography (n = 14), and (iii) IF (n = 14). X-ray exposure (dose–area product [DAP]), injected contrast medium volume, and procedure time were recorded. Results Patient characteristics were similar among groups, with no statistically significant differences (P ≥ .05). There was no statistical difference in endograft deployment success between groups (2D angiography, eight of nine patients [89%]; 3D angiography and IF, 14 of 14 patients each [100%]). The IF group showed significant reduction (P < .0001) in injected contrast medium volume versus other groups (2D, 235 mL ± 145; 3D, 225 mL ± 119; IF, 65 mL ± 28). Mean DAP values showed no significant difference between groups (2D, 1,188 Gy · cm2 ± 1,067; 3D, 984 Gy · cm2 ± 581; IF, 655 Gy · cm2 ± 457; P = .18); nor did procedure times (2D, 233 min ± 123; 3D, 181 min ± 53; IF, 189 min ± 60; P = .59). Conclusions The use of IF-based roadmapping is a feasible technique for endovascular complex aneurysm repair associated with significant reduction of injected contrast agent volume and similar x-ray exposure and procedure time.
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