Complex Analysis of Diffusion Transport and Microstructure of an Intervertebral Disk

Byvaltsev, Vadim A.; Kolesnikov, S. I.; Belykh, Evgenii; Stepanov, I. A.; Bardonova, Liudmila; Судаков, Н. П.; Клименков, И. В.; Никифоров, С. Б.; Семенов, А В; Perfil’ev, D. V.; Bespyatykh, I. V.; Antipina, S. L.; Giers, Morgan B.; Prul, M.

doi:10.1007/s10517-017-3963-z

Cited by 6 publications

(5 citation statements)

References 8 publications

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“… 12 , 13 Lastly, degeneration of the IVD leads to changes in the NP's ECM that altered diffusion kinetics of solutes through the IVD. 14 , 15 , 16 As a result of the changes in IVD biology, diffusion rates decrease dramatically, leading to poor nutrition (ie, glucose and oxygen), high acidity, and high cell death. 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 …”

Section: Introductionmentioning

confidence: 99%

“…12,13 Lastly, degeneration of the IVD leads to changes in the NP's ECM that altered diffusion kinetics of solutes through the IVD. [14][15][16] As a result of the changes in IVD biology, diffusion rates decrease dramatically, leading to poor nutrition (ie, glucose and oxygen), high acidity, and high cell death. [17][18][19][20][21][22][23][24][25][26][27][28][29][30] In addition, clinical stem cell studies reported widely varying cell doses being administered to treat IVD degeneration, ranging from 1 million to 40 million cells per patient as reviewed by Sakai and Schol.…”

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confidence: 99%

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Patient‐specific apparent diffusion maps used to model nutrient availability in degenerated intervertebral discs

et al. 2021

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Introduction: In this study, magnetic resonance imaging data was used to (1) model IVD-specific gradients of glucose, oxygen, lactate, and pH; and (2) investigate possible effects of covariate factors (i.e., disc geometry, and mean apparent diffusion coefficient values) on the IVD's microenvironment. Mathematical modeling of the patient's specific IVD microenvironment could be important when selecting patients for stem cell therapy due to the increased nutrient demand created by that treatment.Materials and Methods: Disc geometry and water diffusion coefficients were extracted from MRIs of 37 patients using sagittal T1-weighted images, T2-weighted images, and ADC Maps. A 2-D steady state finite element mathematical model was developed in COM-SOL Multiphysics ® 5.4 to compute concentration maps of glucose, oxygen, lactate and pH.Results: Concentration of nutrients (i.e., glucose, and oxygen) dropped with increasing distance from the cartilaginous endplates (CEP), whereas acidity levels increased. Most discs experienced poor nutrient levels along with high acidity values in the inner annulus fibrosus (AF). The disc's physiological microenvironment became more deficient as degeneration progressed. For example, minimum glucose concentration in grade 4 dropped by 31.1% compared to grade 3 (p < 0.0001). The model further suggested a strong effect of the following parameters: disc size, AF and CEP diffusivities, metabolic reactions, and cell density on solute concentrations in the disc (p < 0.05). Conclusion:The significance of this work implies that the individual morphology and physiological conditions of each disc, even among discs of the same Pfirrmann grade, should be evaluated when modeling IVD solute concentrations.

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Section: Introductionmentioning

confidence: 99%

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confidence: 99%

Patient‐specific apparent diffusion maps used to model nutrient availability in degenerated intervertebral discs

et al. 2021

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“…4 Based on these efforts, spinal traction does not appear to address nutrient deprivation, requiring innovative new therapies for degeneration. 49 Work by Fields et al explored how changing CEP permeability would influence nutrient diffusion -though nutrient delivery was not clearly improved, this study established a clear correlation. 50 Therefore, this strategy offers a promising new direction for addressing nutrient transport deficits in IVD.…”

Section: Nutrient Considerations In Ivd Therapymentioning

confidence: 71%

Energy Supply and Demand in the Intervertebral Disc

et al. 2018

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The intervertebral disc (IVD) is one of the parts of the body most commonly affected by disease, and it is only recently that we have come closer to understanding the reasons for its degeneration, in which nutrient supply plays a crucial role. In this literature review, we discuss the basic principles and characteristics of energy supply and demand to the IVD. Specifically, we review how different metabolites influence IVD cell activity, the effects of mechanical loading on IVD cell metabolism, and differences in energy metabolism of the annulus fibrous and nucleus pulposus cell phenotypes. Determining the factors that influence nutrient supply and demand in the IVD will enhance our understanding of the IVD pathology, and help to elucidate new therapeutic targets for IVD degeneration treatment.

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“…An IVD is a fibro-cartilaginous joint consisting of the outer concentric cartilaginous lamellae of the annulus fibrosus and an inner deformable proteoglycan-rich nucleus pulposus centered between two cartilage endplates and their connected vertebrae [ 75 , 76 , 77 ]. IVD herniation is the avulsion of the nucleus pulposus through a ruptured annulus fibrosus.…”

Section: Resultsmentioning

confidence: 99%

Molecular and Genetic Mechanisms of Spinal Stenosis Formation: Systematic Review

Byvaltsev

Калинин

Hernandez

et al. 2022

IJMS

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Spinal stenosis (SS) is a multifactorial polyetiological condition characterized by the narrowing of the spinal canal. This condition is a common source of pain among people over 50 years old. We perform a systematic review of molecular and genetic mechanisms that cause SS. The five main mechanisms of SS were found to be ossification of the posterior longitudinal ligament (OPLL), hypertrophy and ossification of the ligamentum flavum (HLF/OLF), facet joint (FJ) osteoarthritis, herniation of the intervertebral disc (IVD), and achondroplasia. FJ osteoarthritis, OPLL, and HLF/OLFLF/OLF have all been associated with an over-abundance of transforming growth factor beta and genes related to this phenomenon. OPLL has also been associated with increased bone morphogenetic protein 2. FJ osteoarthritis is additionally associated with Wnt/β-catenin signaling and genes. IVD herniation is associated with collagen type I alpha 1 and 2 gene mutations and subsequent protein dysregulation. Finally, achondroplasia is associated with fibroblast growth factor receptor 3 gene mutations and fibroblast growth factor signaling. Although most publications lack data on a direct relationship between the mutation and SS formation, it is clear that genetics has a direct impact on the formation of any pathology, including SS. Further studies are necessary to understand the genetic and molecular changes associated with SS.

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Complex Analysis of Diffusion Transport and Microstructure of an Intervertebral Disk

Cited by 6 publications

References 8 publications

Patient‐specific apparent diffusion maps used to model nutrient availability in degenerated intervertebral discs

Patient‐specific apparent diffusion maps used to model nutrient availability in degenerated intervertebral discs

Energy Supply and Demand in the Intervertebral Disc

Molecular and Genetic Mechanisms of Spinal Stenosis Formation: Systematic Review

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