ISSLS Prize Winner: A Study of Effects of In Vivo Mechanical Forces on Human Lumbar Discs With Scoliotic Disc as a Biological Model

Rajasekaran, Shanmuganathan; Vidyadhara, S.; Subbiah, M; Kamath, Vijay; Rajamanickam, Karunanithi; Shetty, Ajoy Prasad; Venkateswaran, Krishna; Babu, Mary; Meenakshi, J.

doi:10.1097/brs.0b013e3181e9a156

Cited by 40 publications

(13 citation statements)

References 73 publications

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“…Eur Spine J (2014) 23:1803-1814 1809 to abnormal environmental (load) stresses which may impact on their gene expression profiles [80,81]. Interestingly, results from microarray studies in our group confirm the presence of some of these proposed immature genes both in mature bovine and adult human NP.…”

Section: Cd239supporting

confidence: 74%

An understanding of intervertebral disc development, maturation and cell phenotype provides clues to direct cell-based tissue regeneration therapies for disc degeneration

2014

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Cell-based regenerative medicine therapies have been proposed for repairing the degenerated intervertebral disc (a major cause of back pain). However, for this approach to be successful, it is essential to characterise the phenotype of its native cells to guarantee that implanted cells differentiate and maintain the correct phenotype to ensure appropriate cell and tissue function. While recent studies have increased our knowledge of the human nucleus pulposus (NP) cell phenotype, their ontogeny is still unclear. The expression of notochordal markers by a subpopulation of adult NP cells suggests that, contrary to previous reports, notochord-derived cells are retained in the adult NP, possibly coexisting with a second population of cells originating from the annulus fibrosus or endplate. It is not known, however, how these two cell populations interact and their specific role(s) in disc homeostasis and disease. In particular, notochordal cells are proposed to display both anabolic and protective roles; therefore, they may be the ideal cells to repair the degenerate disc. Thus, understanding the ontogeny of the adult NP cells is paramount, as it will inform the medical and scientific communities as to the ideal phenotype to implant into the degenerate disc and the specific pathways involved in stem cell differentiation towards such a phenotype.

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Section: Cd239supporting

confidence: 74%

An understanding of intervertebral disc development, maturation and cell phenotype provides clues to direct cell-based tissue regeneration therapies for disc degeneration

2014

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“…Although the solute diffusion behaviors in human CEP were previously studied using the fluorescein-labeled markers and contrast agents (Rajasekaran, et al, 2004; Rajasekaran, et al, 2010; Roberts, et al, 1996), the diffusivity values of basic nutrient/metabolite (i.e., glucose/lactate) in healthy or degenerated human CEP are largely unknown. Glycolysis is believed to be the major energy metabolism pathway for disc cells in vivo by consuming glucose to generate adenosine triphosphate (ATP) and producing lactic acid as a waste product (Bibby, et al, 2005).…”

Section: Introductionmentioning

confidence: 99%

Region and strain-dependent diffusivities of glucose and lactate in healthy human cartilage endplate

Cisewski

Wegner

et al. 2016

Journal of Biomechanics

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The cartilage endplate (CEP) is implicated as the main pathway of nutrient supply to the healthy human intervertebral disc (IVD). In this study, the diffusivities of nutrient/metabolite solutes in healthy CEP were assessed, and further correlated with tissue biochemical composition and structure. The CEPs from non-degenerated human IVD were divided into four regions: central, lateral, anterior, and posterior. The diffusivities of glucose and lactate were measured with a custom diffusion cell apparatus under 0%, 10%, and 20% compressive strains. Biochemical assays were conducted to quantify the water and glycosaminoglycan (GAG) contents. The Safranin-O and Ehrlich’s hematoxylin and eosin staining and scanning electron microscopy (SEM) were performed to reveal the tissue structure of the CEP. Average diffusivities of glucose and lactate in healthy CEP were 2.68±0.93×10−7 cm2/s and 4.52±1.47×10−7 cm2/s, respectively. Solute diffusivities were region-dependent (p<0.0001) with the highest values in the central region, and mechanical strains impeded solute diffusion in the CEP (p<0.0001). The solute diffusivities were significantly correlated with the tissue porosities (glucose: p<0.0001, r=0.581; lactate: p<0.0001, r=0.534). Histological and SEM studies further revealed that the collagen fibers in healthy CEP are more compacted than those in the nucleus pulposus (NP) and annulus fibrosus (AF) and show no clear orientation. Compared to human AF and NP, much smaller solute diffusivities in human CEP suggested that it acts as a gateway for solute diffusion through the disc, maintaining the balance of nutritional environment in healthy human disc under mechanical loading and preventing the progression of disc degeneration.

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“…By contrast, the permeability coefficient of human CEP is found to be about 1/3 and 1/10 of that in human AF and cartilage (Maroudas et al, 1975). Compared with NP and AF tissue, previous studies also indicated that CEP has a unique 3D morphology, inhomogeneous biochemical composition, and regional dependent solute diffusion rate (Fields et al, 2014b; Rajasekaran et al, 2004; Rajasekaran et al, 2008; Rajasekaran et al, 2010; Roberts et al, 1989; Roberts et al, 1996). Therefore, we hypothesized that the biphasic viscoelastic properties of the CEP may also be regional dependent.…”

Section: Introductionmentioning

confidence: 99%

The region-dependent biomechanical and biochemical properties of bovine cartilaginous endplate

Cisewski

Sachs

et al. 2015

Journal of Biomechanics

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Regional biomechanical and biochemical properties of bovine cartilaginous endplate (CEP) and its role in disc mechanics and nutrition were determined. The equilibrium aggregate modulus and hydraulic permeability between the central and lateral regions were examined by confined compression testing. Biochemical assays were conducted to quantify the amount of water, collagen, and glycosaminoglycan (GAG). The equilibrium aggregate modulus of the CEP in the central region (0.23±0.15 MPa) was significantly lower than for the lateral region (0.83±0.26 MPa). No significant regional difference was found for the permeability of the CEP (central region: 0.13±0.07×10−15 m4/Ns and lateral region: 0.09±0.03×10−15 m4/Ns). CEPs were an average of 75.6% water by wet weight, 41.1% collagen, and 20.4% GAG by dry weight in the central region, as well as an average of 70.2% water by wet weight, 73.8% collagen, and 11.7% GAG by dry weight in the lateral region. Regional differences observed for the equilibrium aggregate modulus were likely due to the regional variation in biochemical composition. The lateral bovine endplate is much stiffer and may share a greater portion of the load. Compared with the nucleus pulposus (NP) and annulus fibrosus (AF), a smaller hydraulic permeability was found for the CEP in both the central and lateral regions, which could be due to its lower water content and higher collagen content. Our results suggest that the CEP may block rapid fluid exchange and solute convection, allow pressurization of the interstitial fluid, and play a significant role in nutrient supply in response to loading.

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ISSLS Prize Winner: A Study of Effects of In Vivo Mechanical Forces on Human Lumbar Discs With Scoliotic Disc as a Biological Model

Cited by 40 publications

References 73 publications

An understanding of intervertebral disc development, maturation and cell phenotype provides clues to direct cell-based tissue regeneration therapies for disc degeneration

An understanding of intervertebral disc development, maturation and cell phenotype provides clues to direct cell-based tissue regeneration therapies for disc degeneration

Region and strain-dependent diffusivities of glucose and lactate in healthy human cartilage endplate

The region-dependent biomechanical and biochemical properties of bovine cartilaginous endplate

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