The Role of Cell Clusters in Intervertebral Disc Degeneration and its Relevance behind Repair

Lama, Polly; Kulkarni, Jyoti; Tamang, Binod Kumar

doi:10.21767/2471-8173.100035

Cited by 11 publications

(13 citation statements)

References 62 publications

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“…Another characteristic of NP cells in their native environment is the tendency to cluster into small groups of cells, which have been referred as the “functional units” for disc repair, within the NP [52] , [53] . In order to investigate the clustering tendency of NP cells in our hydrogels the live/dead images were used to analyse the size of the observed cell/cell clusters using an approach used to characterise the distribution of nano-particles (see materials and method for more details).…”

Section: Resultsmentioning

confidence: 99%

Graphene oxide containing self-assembling peptide hybrid hydrogels as a potential 3D injectable cell delivery platform for intervertebral disc repair applications

et al. 2019

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Section: Resultsmentioning

confidence: 99%

Graphene oxide containing self-assembling peptide hybrid hydrogels as a potential 3D injectable cell delivery platform for intervertebral disc repair applications

et al. 2019

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“…Large cellular clusters with locally very high cellular density and loss of the cell‐individual PCM are a common feature of advanced IVD degeneration (Lama, Kulkarni, & Tamang, ). In this study, however, no general change in cellular density was observed between the different degeneration grades ( p = 0.925) with median cell counts of 142 to 239 cells/mm 2 (Table ).…”

Section: Resultsmentioning

confidence: 99%

Chondrocyte death after mechanically overloading degenerated human intervertebral disk explants is associated with a structurally impaired pericellular matrix

Hofmann

Steidle

Danalache

et al. 2018

J Tissue Eng Regen Med

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A type VI collagen-rich pericellular matrix (PCM) encloses both intervertebral disk (IVD) and articular cartilage chondrocytes. In the latter, the PCM protects the chondrocytes from mechanical overload, whereas tissue degeneration is associated with PCM destruction. As little is known about the IVD PCM, we investigated chondrocyte survival after mechanical overload as well as PCM structural integrity as a function of clinical tissue degeneration. The hypothesis was that IVD degeneration may affect PCM integrity and overload-related chondrocyte survival. Cylindrical human IVD explants from patients undergoing surgical procedures for lumbar disk degeneration, disk prolapse, or spinal trauma were generated and scored. Mechanical overload was applied by single uniaxial 50% compression followed by immediate release, and the explants were live-dead stained (n = 20 explants). Type VI collagen, the major PCM component, was fluorescent stained and the extent was determined, in which individual cells were enclosed by a recognizable PCM; this was termed PCM fraction. More than 50% of chondrocytes in all degenerative IVD explants displayed <25% PCM fraction and a lower PCM fraction correlated with higher cell numbers (p < 0.001), suggesting a PCM structural impairment in IVD degeneration that is associated with chondrocyte clustering. Mechanical overload-induced significantly increased cell death (p = 0.005), and the PCM fraction was significantly lower in overload-induced cell death than in live cells (p = 0.042), suggesting that a fully present PCM has a protective role in mechanical overload. Collectively, human IVD degeneration is associated with a structural impairment of the PCM, which may promote cell death under mechanical overload.

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“…The deformation solution of the quadratic tetrahedral (C3D10H) elements in each model was reverse‐engineered to yield Green strain tensors for cell‐sized linear tetrahedral elements (C3D4). These linear tetrahedral elements had an effective seed size (20 μm) that is similar to the size of mature AF cells 47,48 . From the cell‐volume strain tensor, the CME for all cell‐sized volumes in the ROI was categorized as either within (“satisfying”) or outside (“not satisfying”) the proposed target mechanics envelope.…”

Section: Methodsmentioning

confidence: 99%

“…These linear tetrahedral elements had an effective seed size (20 μm) that is similar to the size of mature AF cells. 47 , 48 From the cell‐volume strain tensor, the CME for all cell‐sized volumes in the ROI was categorized as either within (“satisfying”) or outside (“not satisfying”) the proposed target mechanics envelope. These target mechanics were derived from previously published 3D micromechanical criteria for anabolic responses of mature human AF cells.…”

Section: Methodsmentioning

confidence: 99%

High throughput computational evaluation of how scaffold architecture, material selection, and loading modality influence the cellular micromechanical environment in tissue engineering strategies

2021

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Background In tissue engineering (TE) strategies, cell processes are regulated by mechanical stimuli. Although TE scaffolds have been developed to replicate tissue‐level mechanical properties, it is intractable to experimentally measure and prescribe the cellular micromechanical environment (CME) generated within these constructs. Accordingly, this study aimed to fill this lack of understanding by modeling the CME in TE scaffolds using the finite element method. Methods A repeating unit of composite fiber scaffold for annulus fibrosus (AF) repair with a fibrin hydrogel matrix was prescribed a series of loading, material, and architectural parameters. The distribution of CME in the scaffold was predicted and compared to proposed target mechanics based on anabolic responses of AF cells. Results The multi‐axial loading modality predicted the greatest percentage of cell volumes falling within the CME target envelope (%PTE) in the study (65 %PTE for 5.0% equibiaxial tensile strain with 50 kPa radial‐direction compression; 7.6 %PTE without radial pressure). Additionally, the architectural scale had a moderate influence on the CME (maximum of 17 %PTE), with minimal change in the tissue‐level properties of the scaffold. Scaffold materials and architectures had secondary influences on the predicted regeneration by modifying the tissue‐level scaffold mechanics. Conclusions Scaffold loading modality was identified as the critical factor for TE the AF. Scaffold materials and architecture were also predicted to modulate the scaffold loading and, therefore, control the CME indirectly. This study facilitated an improved understanding of the relationship between tissue‐level and cell‐level mechanics to drive anabolic cell responses for tissue regeneration.

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The Role of Cell Clusters in Intervertebral Disc Degeneration and its Relevance behind Repair

Cited by 11 publications

References 62 publications

Graphene oxide containing self-assembling peptide hybrid hydrogels as a potential 3D injectable cell delivery platform for intervertebral disc repair applications

Graphene oxide containing self-assembling peptide hybrid hydrogels as a potential 3D injectable cell delivery platform for intervertebral disc repair applications

Chondrocyte death after mechanically overloading degenerated human intervertebral disk explants is associated with a structurally impaired pericellular matrix

High throughput computational evaluation of how scaffold architecture, material selection, and loading modality influence the cellular micromechanical environment in tissue engineering strategies

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