Cells From Different Regions of the Intervertebral Disc

Horner, Heather A.; Roberts, S.; Bielby, Robert C.; Menage, J.; Evans, Helen H.; Urban, Jill

doi:10.1097/00007632-200205150-00004

Cited by 158 publications

(34 citation statements)

References 58 publications

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“…A potential limitation of the current study is that the use of 2D culture may alter the NP cell phenotype [44], and may differentially regulate the inflammatory response [45]. However, NPs are known to respond to cytokines both in vivo and in vitro [20], and our findings on biophysical responses are assessed on cells in 3D-like rounded morphology.…”

Section: Discussionmentioning

confidence: 97%

Inflammation Induces Irreversible Biophysical Changes in Isolated Nucleus Pulposus Cells

et al. 2014

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Intervertebral disc degeneration is accompanied by elevated levels of inflammatory cytokines that have been implicated in disease etiology and matrix degradation. While the effects of inflammatory stimulation on disc cell metabolism have been well-studied, their effects on cell biophysical properties have not been investigated. The hypothesis of this study is that inflammatory stimulation alters the biomechanical properties of isolated disc cells and volume responses to step osmotic loading. Cells from the nucleus pulposus (NP) of bovine discs were isolated and treated with either lipopolysaccharide (LPS), an inflammatory ligand, or with the recombinant cytokine TNF-α for 24 hours. We measured cellular volume regulation responses to osmotic loading either immediately after stimulation or after a 1 week recovery period from the inflammatory stimuli. Cells from each group were tested under step osmotic loading and the transient volume-response was captured via time-lapse microscopy. Volume-responses were analyzed using mixture theory framework to investigate two biomechanical properties of the cell, the intracellular water content and the hydraulic permeability. Intracellular water content did not vary between treatment groups, but hydraulic permeability increased significantly with inflammatory treatment. In the 1 week recovery group, hydraulic permeability remained elevated relative to the untreated recovery control. Cell radius was also significantly increased both after 24 hours of treatment and after 1 week recovery. A significant linear correlation was observed between hydraulic permeability and cell radius in untreated cells at 24 hours and at 1-week recovery, though not in the inflammatory stimulated groups at either time point. This loss of correlation between cell size and hydraulic permeability suggests that regulation of volume change is disrupted irreversibly due to inflammatory stimulation. Inflammatory treated cells exhibited altered F-actin cytoskeleton expression relative to untreated cells. We also found a significant decrease in the expression of aquaporin-1, the predominant water channel in disc NP cells, with inflammatory stimulation. To our knowledge, this is the first study providing evidence that inflammatory stimulation directly alters the mechanobiology of NP cells. The cellular biophysical changes observed in this study are coincident with documented changes in the extracellular matrix induced by inflammation, and may be important in disease etiology.

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Section: Discussionmentioning

confidence: 97%

Inflammation Induces Irreversible Biophysical Changes in Isolated Nucleus Pulposus Cells

et al. 2014

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“…Currently, tissue engineering of AF mainly involve the use of AF cells [4], [9], [10], chondrocytes [5], or bone marrow stem cells (BMSCs) [3], [6] of various origins. However, due to the ageing of differentiated cells, low cellularity, and the intrinsic phenotype heterogeneity of AF cells, application of AF cells or chondrocytes for AF repair/regeneration is limited [11], [12]. Use of BMSCs, which have been overwhelmingly used and shown effectiveness in AF tissue engineering, also confronts with a problem of limited cell availability (only 0.001–0.01% BMSCs in bone marrow aspirates or marrow tissue) [13].…”

Section: Introductionmentioning

confidence: 99%

Identification of Rabbit Annulus Fibrosus-Derived Stem Cells

Liu

Guo

et al. 2014

PLoS ONE

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Annulus fibrosus (AF) injuries can lead to substantial deterioration of intervertebral disc (IVD) which characterizes degenerative disc disease (DDD). However, treatments for AF repair/regeneration remain challenging due to the intrinsic heterogeneity of AF tissue at cellular, biochemical, and biomechanical levels. In this study, we isolated and characterized a sub-population of cells from rabbit AF tissue which formed colonies in vitro and could self-renew. These cells showed gene expression of typical surface antigen molecules characterizing mesenchymal stem cells (MSCs), including CD29, CD44, and CD166. Meanwhile, they did not express negative markers of MSCs such as CD4, CD8, and CD14. They also expressed Oct-4, nucleostemin, and SSEA-4 proteins. Upon induced differentiation they showed typical osteogenesis, chondrogenesis, and adipogenesis potential. Together, these AF-derived colony-forming cells possessed clonogenicity, self-renewal, and multi-potential differentiation capability, the three criteria characterizing MSCs. Such AF-derived stem cells may potentially be an ideal candidate for DDD treatments using cell therapies or tissue engineering approaches.

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“…The layers in inner AF are thicker than outer AF layers and less hydrated in comparison with NP. 2,3 In outer AF, elongated cells are aligned parallel to collagen I fibers, whereas inner AF consists of spherical cells embedded within the extracellular matrix (ECM). 4 Such regional distinction in cellular morphology and ECM composition play an important role in managing compressive and tensile loads in spinal joints.…”

Section: Introductionmentioning

confidence: 99%

Strategies for Replicating Anatomical Cartilaginous Tissue Gradient in Engineered Intervertebral Disc

Bhattacharjee

Chameettachal²,

Pahwa

et al. 2013

ACS Appl. Mater. Interfaces

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A critical challenge in fabricating a load bearing tissue, such as an intervertebral disc, is to simulate cellular and matrix alignment and anisotropy, as well as a specific biochemical gradient. Towards this goal, multilamellar silk fibroin scaffolds having criss-cross fibrous orientation were developed, where silk fibers in inner layers were crosslinked with bioactive molecule chondroitin sulfate. Upon culturing goat articular chondrocytes under static and dynamic conditions, lamellar scaffold architecture guided alignment of cells and the newly synthesized extracellular matrix (ECM) along the silk fibers. The dynamic culture conditions further improved the cellular metabolic rate and ECM production. Further the synergistic effect of chemical composition of scaffold and hydrodynamic environment of bioreactor contributed in developing a tissue gradient within the constructs, with an inner region rich in collagen II, glycosaminoglycan (GAG), and stiffer in compression, whereas an outer region rich in collagen I and stiffer in tension. Therefore, a unique combination of chemical and physical parameters of engineered constructs and dynamic culture conditions provides a promising starting point to further improve the system towards replicating the anatomical structure, composition gradient, and function of intervertebral disc tissue.

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Cells From Different Regions of the Intervertebral Disc

Cited by 158 publications

References 58 publications

Inflammation Induces Irreversible Biophysical Changes in Isolated Nucleus Pulposus Cells

Inflammation Induces Irreversible Biophysical Changes in Isolated Nucleus Pulposus Cells

Identification of Rabbit Annulus Fibrosus-Derived Stem Cells

Strategies for Replicating Anatomical Cartilaginous Tissue Gradient in Engineered Intervertebral Disc

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