The Role Of Extracellular Matrix Elasticity and Composition In Regulating the Nucleus Pulposus Cell Phenotype in the Intervertebral Disc: A Narrative Review

Hwang, Priscilla Y.; Chen, Jun; Jing, Liufang; Hoffman, Brenton D.; Setton, Lori A.

doi:10.1115/1.4026360

Cited by 81 publications

(83 citation statements)

References 102 publications

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“…Indeed, a prior study by our group has suggested that NP cells prefer attachment to and matrix synthesis upon very soft substrates of ~ 200 Pa stiffness, although those substrates contained laminin-PEG composite hydrogels, rather than HA-PEG as used here [57]. Also, our other prior studies [71, 78] have also demonstrated that soft (<700 Pa), laminin-containing extracellular matrix substrates promote a biosynthetically active and juvenile NP cell phenotype, as measured by NP cell morphology, cell-cell interactions, and proteoglycan production in vitro. Surprisingly, the results in the current study suggest that softer hydrogels formed from HA-PEG were found to be the least favorable substrates for promoting high matrix synthesis as measured by sGAG/DNA and for both cell types.…”

Section: Discussionmentioning

confidence: 99%

Screening of hyaluronic acid–poly(ethylene glycol) composite hydrogels to support intervertebral disc cell biosynthesis using artificial neural network analysis

et al. 2014

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Hyaluronic acid (HA) poly(ethylene glycol) (PEG) composite hydrogels have been widely studied for both cell delivery and soft tissue regeneration applications. A very broad range of physical and biological properties have been engineered into HA-PEG hydrogels that may differentially affect cellular “outcomes” of survival, synthesis and metabolism. The objective of this study was to rapidly screen multiple HA-PEG composite hydrogel formulations for an effect on matrix synthesis and behaviors of nucleus pulposus (NP) and anulus fibrosus (AF) cells of the intervertebral disc (IVD). A secondary objective was to apply artificial neural network (ANN) analysis to identify relationships between HA-PEG composite hydrogel formulation parameters and biological outcome measures for each cell type of the IVD. Eight different hydrogels were developed from preparations of thiolated HA (HA-SH) and PEG vinylsulfone (PEG-VS) macromers, and used as substrates for NP and AF cell culture in vitro. Hydrogel mechanical properties ranged from 70-489 kPa depending on HA molecular weight, and measures of matrix synthesis, metabolite consumption and production, and cell morphology were obtained to study relationships to hydrogel parameters. Results showed that NP and AF cell numbers were highest upon the HA-PEG hydrogels formed from the lower molecular weight HA, with evidence of higher sGAG production also upon lower HA molecular weight composite gels. All cells formed more multi-cell clusters upon any HA-PEG composite hydrogel as compared to gelatin substrates. Formulations were clustered into neurons based largely on their HA molecular weight, with few effects of PEG molecular weight observed on any measured parameters.

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Section: Discussionmentioning

confidence: 99%

Screening of hyaluronic acid–poly(ethylene glycol) composite hydrogels to support intervertebral disc cell biosynthesis using artificial neural network analysis

et al. 2014

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“…Much work has been done in the field to study NP cell characteristics in IVD tissue of various species, specifically how NP cell characteristics change with age (with matrix elasticity values from 0.3 up to 5 kPa 11,26,27 ). Juvenile NP cells have been characterized via the presence of brachyury-T 44 and production of extracellular matrix molecules (aggrecan, type II collagen, and laminin β 1).…”

Section: Introductionmentioning

confidence: 99%

N-Cadherin-Mediated Signaling Regulates Cell Phenotype for Nucleus Pulposus Cells of the Intervertebral Disc

et al. 2014

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Juvenile nucleus pulposus (NP) cells of the intervertebral disc (IVD) are large, vacuolated cells that form cell clusters with strong cell–cell interactions. With maturation and aging, NP cells lose their ability to form these cell clusters, with aging-associated changes in NP cell phenotype, morphology, and proteoglycan synthesis that may contribute to IVD degeneration. Therefore, it is important to understand the mechanisms governing juvenile NP cell cluster behavior towards the goal of revealing factors that can promote juvenile, healthy NP cell phenotypes. N-cadherin has been identified as a cell–cell adhesion marker that is present in juvenile NP cells, but disappears with age. The goal of this study was to reveal the importance of N-cadherin in regulating cell–cell interactions in juvenile NP cell cluster formation and test for a regulatory role in maintaining a juvenile NP phenotype in vitro. Juvenile porcine IVD cells, of notochordal origin, were promoted to form cell clusters in vitro, and analyzed for preservation of the juvenile NP phenotype. Additionally, cadherin-blocking experiments were performed to prevent cluster formation in order to study the importance of cluster formation in NP cell signaling. Findings reveal N-cadherin-mediated cell–cell contacts promote cell clustering behavior and regulate NP cell matrix production and preservation of NP-specific markers. Inhibition of N-cadherin-mediated contacts resulted in loss of all features of the juvenile NP cell. These results establish a regulatory role for N-cadherin in juvenile NP cells, and suggest that preservation of the N-cadherin mediated cell–cell contact is important for preserving juvenile NP cell phenotype and morphology.

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“…Furthermore, loss of NP proteoglycan matrix coupled with an increased content of nonaggregating proteoglycan breakdown products attenuates the hygroscopic properties of ECM, resulting in reduced water content, swelling pressure and ability to withstand load. Dehydration of the NP also inhibits the availability of nutrients and growth factors to the disc cells, leading to further impairment of IVD function [28].…”

Section: Matrix Synthesis and Degradation During Disc Degenerationmentioning

confidence: 99%

MMPs and ADAMTSs in intervertebral disc degeneration

Wang

et al. 2015

Clinica Chimica Acta

164

124

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The Role Of Extracellular Matrix Elasticity and Composition In Regulating the Nucleus Pulposus Cell Phenotype in the Intervertebral Disc: A Narrative Review

Cited by 81 publications

References 102 publications

Screening of hyaluronic acid–poly(ethylene glycol) composite hydrogels to support intervertebral disc cell biosynthesis using artificial neural network analysis

Screening of hyaluronic acid–poly(ethylene glycol) composite hydrogels to support intervertebral disc cell biosynthesis using artificial neural network analysis

N-Cadherin-Mediated Signaling Regulates Cell Phenotype for Nucleus Pulposus Cells of the Intervertebral Disc

MMPs and ADAMTSs in intervertebral disc degeneration

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