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Relevant bibliographies by topics / Intervertebral Disc Regeneration

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Academic literature on the topic 'Intervertebral Disc Regeneration'

Author: Grafiati

Published: 25 May 2024

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Journal articles on the topic "Intervertebral Disc Regeneration"

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Ju, Derek G., Linda E. Kanim, and Hyun W. Bae. "Intervertebral Disc Repair: Current Concepts." Global Spine Journal 10, no. 2_suppl (April 2020): 130S—136S. http://dx.doi.org/10.1177/2192568219872460.

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Study Design: Review article. Objective: A review of the literature on current strategies utilized in intervertebral regeneration and repair efforts. Methods: A review of the literature and analysis of the data to provide an updated review on current concepts of intervertebral disc repair and regeneration efforts. Results: Multiple regenerative strategies for intervertebral disc regeneration are being employed to reduce pain and improve quality of life. Current promising strategies include molecular therapy, gene therapy, cell-based therapy, and augmentation with biomaterials. Multiple clinical trials studying biologic, cell-based, and scaffold-based injectable therapies are currently being investigated. Conclusion: Low back pain due to intervertebral disc disease represents a significant health and societal burden. Current promising strategies include molecular therapy, gene therapy, cell-based therapy, and augmentation with biomaterials. To date, there are no Food and Drug Administration–approved intradiscal therapies for discogenic back pain, and there are no large randomized trials that have shown clinically significant improvement with any investigational regenerative treatment. Multiple clinical trials studying biologic, cell-based, or scaffold-based injectable therapies are being currently investigated.

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Johnson, W. E. B., and S. Roberts. "‘Rumours of my death may have been greatly exaggerated’: a brief review of cell death in human intervertebral disc disease and implications for cell transplantation therapy." Biochemical Society Transactions 35, no. 4 (July 20, 2007): 680–82. http://dx.doi.org/10.1042/bst0350680.

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The avascular nature of the human intervertebral disc is thought to reduce the ability of resident disc cells to maintain their extracellular matrix, rendering the tissue susceptible to degeneration. It has also been suggested that the lack of a blood supply may result in disc cell death via nutrient deprivation. Therefore transplanting new cells into the disc to promote tissue regeneration would be akin to ‘putting cells in a coffin’ and doomed to failure. This review considers the available evidence for cell death in the human intervertebral disc, describing briefly the methods used to assay such death, and concludes that further analysis is required to ascertain whether extensive cell death truly is a marked feature of human intervertebral discs and whether it bears any relationship to disc degeneration and hence regenerative strategies.

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Yan, Caiping, Xingkuan Wang, Chao Xiang, Yong Wang, Chaoyu Pu, Lu Chen, Ke Jiang, and Yuling Li. "Applications of Functionalized Hydrogels in the Regeneration of the Intervertebral Disc." BioMed Research International 2021 (August 19, 2021): 1–19. http://dx.doi.org/10.1155/2021/2818624.

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Intervertebral disc degeneration (IDD) is caused by genetics, aging, and environmental factors and is one of the leading causes of low back pain. The treatment of IDD presents many challenges. Hydrogels are biomaterials that possess properties similar to those of the natural extracellular matrix and have significant potential in the field of regenerative medicine. Hydrogels with various functional qualities have recently been used to repair and regenerate diseased intervertebral discs. Here, we review the mechanisms of intervertebral disc homeostasis and degeneration and then discuss the applications of hydrogel-mediated repair and intervertebral disc regeneration. The classification of artificial hydrogels and natural hydrogels is then briefly introduced, followed by an update on the development of functional hydrogels, which include noncellular therapeutic hydrogels, cellular therapeutic hydrogel scaffolds, responsive hydrogels, and multifunctional hydrogels. The challenges faced and future developments of the hydrogels used in IDD are discussed as they further promote their clinical translation.

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Bodnarchuk, J. A., M. V. Khyzhnjak, О. О. Potapov, and N. G. Chopik. "BIOCHEMICAL AND BIOMECHANICAL SUBSTANTIATION OF REPARATIVE REGENERATION OF INTERVERTEBRAL DISCS IN PATIENTS WITH DEGENERATIVE DISC DISEASES." Eastern Ukrainian Medical Journal 8, no. 3 (2020): 249–54. http://dx.doi.org/10.21272/eumj.2020;8(3):249-254.

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Degenerative disc diseases occupy the second place in the overall structure of morbidity with temporary disability. In 40% of patients with spinal osteochondrosis, diseases of the locomotor apparatus and connective tissue cause primary disability. Disc degeneration is a pathological process that is the main cause of low back pain and is observed in the vast majority of people at some point in their lives. The influence of mechanical stress leads to degenerative changes in the tissues of the nucleus pulposus of the intervertebral disc. Limited transport and low cellular saturation of the discs hinder recovery, make the intervertebral disc particularly vulnerable to injury, and contribute to the appearance of morphological tissue damage associated with the processes of biological aging. The pathological process involves all structural elements of the intervertebral disc. The earliest manifestations of disc degeneration usually occur in the nucleus pulposus, where a reduced content of proteoglycans disrupts mechanical function, which leads to progressive morphological degeneration of the entire intervertebral segment. Existing treatment methods (both surgical and conservative) are not able to adjust the number of cells in the nucleus pulposus and are unable to stop the pathological process in the intervertebral disc. Prevention of degeneration or repair of the intervertebral disc is a potential treatment for lumbar pain syndromes. Cell therapy has become a subject of great interest, as new research reports significant regenerative potential for many cellular sources, including the regeneration of the nucleus pulposus region of the intervertebral disc. The use and implementation of modern cell therapy in practical neurosurgery allows us to approach the problem of intervertebral disc degeneration at a new qualitative level with the use of multipotent cells, biochemical peptides in the reparative processes of the nucleus pulposus, as a possibility of treatment and prevention of vertebrogenic pain syndromes in the future. Keywords intervertebral disc, nucleus pulposus, cell therapy, transplantation, degenerative changes, reparation

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Sheikh, Hormoz, Karen Zakharian, Ramiro Perez De La Torre, Christopher Facek, Adrian Vasquez, G. Rasul Chaudhry, David Svinarich, and Mick J. Perez-Cruet. "In vivo intervertebral disc regeneration using stem cell–derived chondroprogenitors." Journal of Neurosurgery: Spine 10, no. 3 (March 2009): 265–72. http://dx.doi.org/10.3171/2008.12.spine0835.

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Object There is currently no biologic therapy to repair or restore a degenerated intervertebral disc. A potential solution may rest with embryonic stem cells (ESCs), which have a potential to grow indefinitely and differentiate into a variety of cell types in vitro. Prior studies have shown that ESCs can be encouraged to differentiate toward specific cell lineages by culture in selective media and specific growth environment. Among these lineages, there are cells capable of potentially producing nucleus pulposus (NP) in vivo. In this investigation, the authors studied ESCderived chondroprogenitors implanted into a degenerated disc in a rabbit. For this purpose, a rabbit model of disc degeneration was developed. Methods A percutaneous animal model of disc degeneration was developed by needle puncture of healthy intact discs in 16 New Zealand white rabbits. Series of spine MR imaging studies were obtained before disc puncture and after 2, 6, and 8 weeks. Prior to implantation, murine ESCs were cultured with cis-retinoic acid, transforming growth factor β, ascorbic acid, and insulin-like growth factor to induce differentiation toward a chondrocyte lineage. After confirmation by MR imaging, degenerated disc levels were injected with chondrogenic derivatives of ESCs expressing green fluorescent protein. At 8 weeks post-ESC implantation, the animals were killed and the intervertebral discs were harvested and analyzed using H & E staining, confocal fluorescent microscopy, and immunohistochemical analysis. Three intervertebral disc groups were analyzed in 16 rabbits, as follows: 1) Group A, control: naïve, nonpunctured discs (32 discs, levels L4–5 and L5–6); 2) Group B, experimental control: punctured disc (16 discs, level L2–3); and 3) Group C, experimental: punctured disc followed by implantation of chondroprogenitor cells (16 discs, level L3–4). Results The MR imaging studies confirmed intervertebral disc degeneration at needle-punctured segments starting at ~ 2 weeks. Postmortem H & E histological analysis of Group A discs showed mature chondrocytes and no notochordal cells. Group B discs displayed an intact anulus fibrosus and generalized disorganization within fibrous tissue of NP. Group C discs showed islands of notochordal cell growth. Immunofluorescent staining for notochordal cells was negative for Groups A and B but revealed viable notochordal-type cells within experimental Group C discs, which had been implanted with ESC derivatives. Notably, no inflammatory response was noted in Group C discs. Conclusions This study illustrates a reproducible percutaneous model for studying disc degeneration. New notochordal cell populations were seen in degenerated discs injected with ESCs. The lack of immune response to a xenograft of mouse cells in an immunocompetent rabbit model may suggest an as yet unrecognized immunoprivileged site within the intervertebral disc space.

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Bhanushali, Riya. "Regeneration Potential of Stem Cell in the Treatment of IVD." International Journal for Research in Applied Science and Engineering Technology 9, no. 8 (August 31, 2021): 3022–36. http://dx.doi.org/10.22214/ijraset.2021.37908.

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Abstract: Degenerative disc disease is a prevalent musculoskeletal disorder in which damaged spinal discs cause pain upon aging, accidental injuries. Spinal discs connect adjacent vertebrae and help in maintaining mobility, flexibility and rotation of spinal cord. Spinal discs also act as shock absorbers. Intervertebral disc (IVD) degeneration is often associated with low back and neck pain, which accounts for disability worldwide. Physical therapy, spinal fusion surgeries reduce severity and symptoms of degenerative disc disease but they are not complete cure for this disease. Current preclinical studies show that mesenchymal stem cells have the capacity to repair degenerative disks by differentiation to chondrocyte-like cells, which produce proteoglycans and type II collagen. Mesenchymal stem cells (MSCs) isolated from bone marrow (BM-MSCs), adipose tissue (AD-MSCs) and umbilical cord (UC-MSCs) show potential use in cartilage and intervertebral disc (IVD) repair. Regenerative medicine and stem cell therapy hold great promise for treatment of intervertebral disc (IVD) disease. This review discusses about progression of degenerative disc disease, various types of stem cells, potential use of mesenchymal stem cells (MSCs) and embryonic stem cells (ESCs) for the treatment of degenerative disc disease. This review also focuses upon challenges encountered by the application of stem cell therapy for treating degenerative disc disease as well as future perspectives. Keywords: IVD, Stem cell therapy, AF & NP cells, MSCs, Scaffolds, Cell therapy

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Desai, Shivam U., Sai Sadhananth Srinivasan, Sangamesh Gurappa Kumbar, and Isaac L. Moss. "Hydrogel-Based Strategies for Intervertebral Disc Regeneration: Advances, Challenges and Clinical Prospects." Gels 10, no. 1 (January 15, 2024): 62. http://dx.doi.org/10.3390/gels10010062.

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Millions of people worldwide suffer from low back pain and disability associated with intervertebral disc (IVD) degeneration. IVD degeneration is highly correlated with aging, as the nucleus pulposus (NP) dehydrates and the annulus fibrosus (AF) fissures form, which often results in intervertebral disc herniation or disc space collapse and related clinical symptoms. Currently available options for treating intervertebral disc degeneration are symptoms control with therapy modalities, and/or medication, and/or surgical resection of the IVD with or without spinal fusion. As such, there is an urgent clinical demand for more effective disease-modifying treatments for this ubiquitous disorder, rather than the current paradigms focused only on symptom control. Hydrogels are unique biomaterials that have a variety of distinctive qualities, including (but not limited to) biocompatibility, highly adjustable mechanical characteristics, and most importantly, the capacity to absorb and retain water in a manner like that of native human nucleus pulposus tissue. In recent years, various hydrogels have been investigated in vitro and in vivo for the repair of intervertebral discs, some of which are ready for clinical testing. In this review, we summarize the latest findings and developments in the application of hydrogel technology for the repair and regeneration of intervertebral discs.

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Ylinen, P., R. M. Tulamo, M. Kellomäki, P. Türmälä, P. Rokkanen, and T. Palmgren. "Lumbar intervertebral disc replacement using bioabsorbable self-reinforced poly-L-lactide full-threaded screws, or cylindrical implants of polylactide polymers, bioactive glass and Polyactive™." Veterinary and Comparative Orthopaedics and Traumatology 16, no. 03 (July 2003): 138–44. http://dx.doi.org/10.1055/s-0038-1632777.

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SummaryIntervertebral disc surgery leads to changes in the segmental anatomy and mobility, and subsequently to degenerative changes in the lumbar spine. Artificial intervertebral disc implants sufficient to replace the human lumbar intervertebral disc have been developed and the requirements for these defined. This is to our knowledge the first study on bioabsorbable intervertebral disc replacement implants. SR-PLLA screws, previously used in orthopaedic internal fixations, and cylindrical implants, specifially developed for this experimental preliminary study, were used to replace lumbar intervertebral discs of growing pigs. After a 15-week follow-up period, the radiological and histological changes in the intervertebral spaces were analyzed. The cylindrical implants were able to prevent narrowing of discectomied spaces, and tissue regeneration in the intervertebral space was induced and occured simultaneously with degradation of the implant.

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Zhang, Hua, Wei Li, YaoHong Wu, Shengquan Zhang, Jie Li, Letian Han, Haoyu Chen, et al. "Effects of Changes in Osmolarity on the Biological Activity of Human Normal Nucleus Pulposus Mesenchymal Stem Cells." Stem Cells International 2022 (April 23, 2022): 1–15. http://dx.doi.org/10.1155/2022/1121064.

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The expansion and maintenance of the NPMSC (nucleus pulposus mesenchymal stem cell) phenotype are considered as potential therapeutic tools for clinical applications in intervertebral disc tissue engineering and regenerative medicine. However, the harsh microenvironment within the intervertebral disc is the main limitation of its regeneration. The osmolarity of the intervertebral disc is higher than that of other tissues, which has an important influence on the biological characteristics of NPMSCs. In this study, we observed the effect of different osmolarities on the biological characteristics of human normal NPMSCs cultured in vitro and explored the role of osmolarity in intervertebral disc degeneration. Our data demonstrated that the change in osmotic pressure has an important effect on the biological activity of NPMSCs, and this effect may occur through the P16INK4A/Rb pathway. This study provides a theoretical basis for the future treatment of intervertebral disc degeneration.

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Fiordalisi, MF, AJ Silva, M. Barbosa, RM Gonçalves, and J. Caldeira. "Intervertebral disc decellularisation: progress and challenges." European Cells and Materials 42 (October 6, 2021): 196–219. http://dx.doi.org/10.22203/ecm.v042a15.

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Intervertebral disc (IVD) degeneration and the consequent low-back pain (LBP) affect over 80 % of people in western societies, constituting a tremendous socio-economic burden worldwide and largely impairing patients’ life quality. Extracellular matrix (ECM)-based scaffolds, derived from decellularised tissues, are being increasingly explored in regenerative medicine for tissue repair. Decellularisation plays an essential role for host cells and antigen removal, while maintaining native microenvironmental signals, including ECM structure, composition and mechanical properties, which are essential for driving tissue regeneration. With the lack of clinical solutions for IVD repair/regeneration, implantation of decellularised IVD tissues has been explored to halt and/or revert the degenerative cascade and the associated LBP symptoms. Over the last few years, several researchers have focused on the optimisation of IVD decellularisation methods, combining physical, chemical and enzymatic treatments, in order to successfully develop a cell-free matrix. Recellularisation of IVD-based scaffolds with different cell types has been attempted and numerous methods have been explored to address proper IVD regeneration. Herein, the advances in IVD decellularisation methods, sterilisation procedures, repopulation and biocompatibility tests are reviewed. Additionally, the importance of the donor profile for therapeutic success is also addressed. Finally, the perspectives and major hurdles for clinical use of the decellularised ECM-based biomaterials for IVD are discussed. The studies reviewed support the notion that tissue-engineering-based strategies resorting to decellularised IVD may represent a major advancement in the treatment of disc degeneration and consequent LBP.

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Dissertations / Theses on the topic "Intervertebral Disc Regeneration"

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Ho, Grace, and 何秀慧. "Intervertebral disc regeneration by use of autologous mesenchymal stemcells." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2005. http://hub.hku.hk/bib/B31541616.

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Ho, Grace. "Intervertebral disc regeneration by use of autologous mesenchymal stem cells." Click to view the E-thesis via HKUTO, 2005. http://sunzi.lib.hku.hk/hkuto/record/B31541616.

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Yang, Fan. "Intervertebral disc regeneration using mesenchymal stem cells a mouse model study /." Click to view the E-thesis via HKUTO, 2007. http://sunzi.lib.hku.hk/HKUTO/record/B39556979.

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楊帆 and Fan Yang. "Intervertebral disc regeneration using mesenchymal stem cells: a mouse model study." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2007. http://hub.hku.hk/bib/B39556979.

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Choy, Tsz-hang Andrew, and 蔡子鏗. "Fabrication of a biphasic scaffold for tissue engineering of intervertebral disc." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2012. http://hub.hku.hk/bib/B49799459.

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Current treatments to intervertebral disc degeneration alter spine biomechanics and have complications. Tissue engineering offers an approach to regenerate a biological disc that provides flexibility and stability to, and integrates with the spine. To date, a scaffold that mimics the extracellular matrix composition and mechanical strength of a native disc is lacked. In this project, a biphasic scaffold was fabricated using glycosaminoglycan (GAG) and collagen, the prevalent ma-trix components in a native disc. It also adapted the structure of the disc, with la-mellae of collagen surrounding a collagen-GAG (CG) core. The first part of this project studied chemical modification of CG and evaluated the physiochemical and biological properties of modified CGs. As only loosely bound by GAG under physiological environment, collagen was modified by deamination, methylation and amination, and yielded Deaminated, Methylated and Aminated CGs upon co-precipitation with GAG. While GAG was mostly lost within 1 day in Untreated and Deaminated CGs, 20% and 40% GAG was retained after 6 days in Methylated and Aminated CGs respectively. In cell-seeded Aminated CG, over 60% GAG was retained after 8 days. Aminated CG, having the highest GAG/HYP of 4.5, best simulated the GAG-rich nucleus pulposus tissue. In ultrastructural analysis, Aminated CG consisted of abundant granular sub-stances that resembled the nucleus pulposus. Despite the differential initial number adhered to the CG scaffolds, human mesenchymal stem cells (hMSCs) had over 90% viability at all time points. Cell morphology was distinct, being round in Untreated and Methylated CGs but elongated in Deaminated and Aminated ones. The adhesion of hMSCs via collagen receptor, integrin alpha2beta1, was observed in all CG scaffolds, while adhesion via general matrix receptor, integrin alphaV, was extensive in all but Aminated CG. Based on improved GAG incor-poration and retention, which approximate the matrix composition of nucleus pulposus, Aminated CG was chosen as the core of the biphasic scaffold. The second part of this project studied lamination in biphasic disc scaffold and evaluated its mechanical properties in creep, recovery and dynamic loadings. A process was optimized to encapsulate a CG under physiological condition whilst producing an intact collagen gel, which allowed the CG to retain more GAGs and to be confined by the annulus structurally as was in the disc. This encasing approach was repeated for multiple lamellae, one lamella per day. Scaffolds with more lamellae had increased viscous compliance in creep and recovery, which was explained by the less laminated scaffolds being overloaded. Another lamination approach replaced most encasing lamellae with coiling ones. Despite low sample size, it was shown that this combined approach produced scaffolds with lower elastic and viscous compliances and longer equilibrating time in both creep and recovery, and higher complex modulus under dynamic loading. Full recovery was not achieved by any scaffold. This study demonstrated that a biphasic disc scaffold, made of GAG and collagen, contained similar matrix components to native disc, was almost mechanically comparable to the disc, and was cyto-compatible. It paved way towards tissue engineering of intervertebral disc and the intervertebral disc motion segment.
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Mechanical Engineering
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Khan, Shahnaz. "The effect of the intervertebral disc microenvironment on disc cell and mesenchymal stem cell behaviour : implications for disc degeneration and regeneration." Thesis, University of Manchester, 2013. https://www.research.manchester.ac.uk/portal/en/theses/the-effect-of-the-intervertebral-disc-microenvironment-on-disc-cell-and-mesenchymal-stem-cell-behaviour-implications-for-disc-degeneration-and-regeneration(b5629a75-4cb0-45d8-affb-2b936d9408e1).html.

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Intervertebral disc (IVD) degeneration is associated with low back pain (LBP). It has been suggested that changes in the IVD physio-chemical microenvironment (i.e. hypoxia, reduced nutrient and acidic conditions) may lead to disc degeneration. Studying the response of human nucleus pulposus (NP) cells to these conditions could establish the causal relationship between IVD microenvironment and aberrant cellular behaviour, characteristic of disc degeneration. Human bone marrow mesenchymal stem cells (BM-MSCs) are a promising cell population for disc regeneration. However, knowledge of their survival and functioning in the microenvironment of the IVD is still lacking. Moreover, in vitro co-culture model studies that are used to study MSC/disc cell interaction, also need to consider the effect of the microenvironment on cellular responses. BM-MSCs and degenerate NP cells were cultured alone or co-cultured in monolayer under hypoxia (2%O2), reduced nutritional (2% serum or/and 5mM glucose) and acidic (moderate pH 6.8 or severe pH 6.5) conditions alone or in combination for 7 days. Cell viability, proliferation, gene and protein expression was assessed. Degenerate NP cells and BM-MSCs maintained good cell viability under all conditions. Both cell types demonstrated overall similar proliferation and gene and protein responses under the majority of the conditions and combinations studied. Hypoxia promoted aggrecan and versican matrix biosynthesis in both cell types. Nutrient deprived and moderate acidic conditions (pH 6.8) inhibited proliferation of both cell types. Interestingly the combination of hypoxia with these conditions showed a protective effect in modulating cell proliferation. These results imply that hypoxia may be beneficial in some instances. Nutrient deprived conditions had a relatively minor effect on degenerate NP cell gene and protein expression but these conditions specifically inhibited VCAN expression in BM-MSCs. The combination of hypoxia with these conditions increased or restored VCAN expression. Interestingly the combination of hypoxia with reduced glucose conditions increased aggrecan and versican matrix biosynthesis in both NP cells and BM-MSCs. The combination of hypoxia and complete nutrient deprived conditions (both reduced serum and reduced glucose) impaired ACAN, VCAN and PAX-1 gene and aggrecan and versican protein expression in degenerate NP cells implicating disc hypoxia and complete nutrient deprived combined microenvironment in accelerating degenerate changes in NP cells. In contrast, these conditions showed no such detrimental effects on BM-MSC gene and protein expression. pH 6.5 was critical for both cell types proliferation and ACAN and VCAN gene expression suggesting that severe acidic conditions may exacerbate degenerative changes and be inhibitory for implanted MSCs. Finally, a combination of hypoxia, complete nutrient deprived and moderate acidic conditions, reduced cell proliferation without affecting the gene expression profile of both cell types. IVD-like physio-chemical microenvironmental conditions also appeared to influence differentiation of BM-MSC and modulation of degenerate NP cell phenotype observed during co-culture. Noticeably hypoxia, reduced serum or reduced glucose conditions stimulated BM-MSC differentiation and modulation of degenerate NP cell phenotype. Hypoxia also increased or recovered changes at gene expression level in both BM-MSCs and degenerate NP cells under nutrient deprived (reduced serum or/and reduced glucose) conditions during co-culture. Degenerate NP cell and BM-MSC co-culture also showed noticeable increase in aggrecan and versican biosynthesis under hypoxia and reduced glucose combine conditions, implicating these in improving the co-culture responses. Severe pH condition alone, pH 6.8 in combination with hypoxia and finally all IVD-like physio-chemical conditions together compromised co-culture responses. Such results imply that IVD-like physio-chemical microenvironmental conditions may influence MSC based regenerative outcomes. This work has increased our understanding about the influence of disc harsh microenvironment on degeneration and regeneration processes.

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Rodrigues, Pinto Ricardo Pedro Ferreira. "Isolation and phenotypic characterisation of human notochordal cells : implications for the development of cell-based therapies for intervertebral disc degeneration." Thesis, University of Manchester, 2015. https://www.research.manchester.ac.uk/portal/en/theses/isolation-and-phenotypic-characterisation-of-human-notochordal-cells-implications-for-the-development-of-cellbased-therapies-for-intervertebral-disc-degeneration(8d5cbfdd-edd0-458c-a048-554f6a2c830b).html.

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Back pain is a highly prevalent condition whose pathogenesis is associated with intervertebral disc (IVD) degeneration. Degeneration is driven by abnormal cell biology, particularly within the IVD’s inner core, the nucleus pulposus (NP). In recent years, there has been an ever-increasing search for cell-based therapies aimed at correcting the cell biology and thus repairing/regenerating the degenerate IVD. The success of these novel therapies, however, requires a thorough understanding of IVD development and of the phenotype of its cells. The embryonic, foetal and juvenile NP is populated by large vacuolated notochordal cells that with skeletal maturity are replaced by smaller NP cells. Since notochordal cells have been shown to display protective and anabolic roles in the IVD their loss in humans has often been suggested to initiate the degenerative process. As such, a detailed understanding of notochordal cells and their regulatory pathways may help identify factors involved in IVD homeostasis and aid the development of novel cell-based therapies targeting IVD degeneration. The study of human notochordal cells has, however, been hindered by ethical, logistical and technical difficulties in obtaining suitable samples and, as such, the human notochordal cell phenotype is, to date, unknown, constituting a major limitation in the field. The work presented here was conducted with the objective of developing a methodology to isolate human developing notochordal cells (NP progenitors) from adjacent sclerotomal cells (annulus fibrosus and vertebral body progenitors), to characterise the notochordal cell phenotype and identify potential factors involved in notochordal cell biology. Initially, human embryonic and foetal spines were characterised to assess their suitability as a source of notochordal cells and to identify a notochord-specific marker that could be used to isolate notochordal cells for microarray studies. The human developing spine contained large vacuolated notochordal cells in all stages analysed (3.5-18 weeks post-conception (WPC)) that specifically expressed KRT8, KRT18 and KRT19 at all stages and CD24 between 5.5-18 WPC. KRT18 and CD24 were independently used to label notochordal cells (7.5-14 weeks post-conception) and separate them from sclerotomal cells. Methodologies were developed to allow extraction of RNA of sufficient quality for microarray analysis from fixed, permeabilised (in the case of KRT18) and/or, labelled and sorted cells (CD24). Microarray analysis identified and real-time qPCR and, for some markers, immunohistochemistry, validated GRB14, SLC19A1, FGF10, ADORA3, TBXA2R, CDH6, ANPEP, CD69, CD24, RTN1, PRPH, MAP1B, ISL1 and CLDN1 as human notochordal cell markers. Ingenuity pathway analysis was performed to investigate the pathways/networks and upstream regulators and downstream effectors of notochordal cells. Inhibition of inflammation and angiogenesis were identified as relevant to notochordal cell biology, function and, possibly, to the known protective and anabolic role notochordal cells display in the IVD. Notochordal marker gene expression was identified in adult NP tissue, and negatively correlated with degeneration. Proteins encoded by ADORA3 and MAP1B were expressed by a proportion of adult NP cells, suggesting the presence of notochord-derived cells in the adult NP.Importantly, this is the first study to detail a methodology and successfully isolate human notochordal cells. Such methodology has the potential to be used to culture and investigate the biology of viable human notochordal cells (CD24+ve). Future studies aimed at developing cell-based therapies for IVD degeneration could also use these identified markers to assess appropriate stem cell differentiation to notochordal cells.

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Strassburg, Sandra. "An In Vitro Culture System to Study Human Mesenchymal Stem Cell / Nucleus Pulposus Cell Interactions : Implications for Intervertebral Disc Regeneration." Thesis, University of Manchester, 2010. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.521587.

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Aladin, Kaderbatcha Darwesh Mohideen. "Nanoscale structure-property and macroscale biomechanical function of nucleus pulposus in health, disease and regeneration." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2010. http://hub.hku.hk/bib/B45197143.

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Figueiró, Manuela. "Análise histológica, imunohistoquímica e isolamento de células-tronco mesenquimais adultas do disco intervertrebal degenerado aplicadas a medicina regenerativa." reponame:Repositório Institucional da UCS, 2014. https://repositorio.ucs.br/handle/11338/915.

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Books on the topic "Intervertebral Disc Regeneration"

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Grad, Sibylle, Mauro Alini, David Eglin, Daisuke Sakai, Joji Mochida, Sunil Mahor, Estelle Collin, Biraja Dash, and Abhay Pandit. Cells and Biomaterials for Intervertebral Disc Regeneration. Cham: Springer International Publishing, 2010. http://dx.doi.org/10.1007/978-3-031-02580-8.

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Intervertebral Disc Regeneration. MDPI, 2022. http://dx.doi.org/10.3390/books978-3-0365-2755-0.

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Gantenbein, Benjamin, ed. Intervertebral Disc Regeneration II. MDPI, 2023. http://dx.doi.org/10.3390/books978-3-0365-8199-6.

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Grad, Sibylle, Mauro Alini, David Eglin, and Daisuke Sakai. Cells and Biomaterials for Intervertebral Disc Regeneration. Morgan & Claypool Publishers, 2010.

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Grad, Sibylle, Mauro Alini, David Eglin, and Daisuke Sakai. Cells and Biomaterials for Intervertebral Disc Regeneration. Springer International Publishing AG, 2010.

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Cells and Biomaterials for Intervertebral Disc Regeneration. Morgan & Claypool Publishers, 2010.

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Hartl, Roger, and Larry Bonassar. Biological Approaches to Spinal Disc Repair and Regeneration for Clinicians. Thieme Medical Publishers, Incorporated, 2017.

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Shine, Kristy Melissa. Tissue engineering of the intervertebral disc: A scaffold-based approach to nucleus pulposus regeneration. 2009.

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Book chapters on the topic "Intervertebral Disc Regeneration"

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Gazit, Zulma, Nadav Kimelman-Bleich, Olga Mizrahi, and Dan Gazit. "Gene Therapy Approaches for Disc Regeneration." In The Intervertebral Disc, 385–400. Vienna: Springer Vienna, 2013. http://dx.doi.org/10.1007/978-3-7091-1535-0_24.

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Sakai, Daisuke, and Joji Mochida. "Use of Stem Cells for Regeneration of the Intervertebral Disc." In The Intervertebral Disc, 373–83. Vienna: Springer Vienna, 2013. http://dx.doi.org/10.1007/978-3-7091-1535-0_23.

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Grad, Sibylle, Mauro Alini, Daisuke Sakai, and Joji Mochida. "Cell Therapy for Nucleus Pulposus Regeneration." In Cells and Biomaterials for Intervertebral Disc Regeneration, 1–42. Cham: Springer International Publishing, 2010. http://dx.doi.org/10.1007/978-3-031-02580-8_1.

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Mahor, Sunil, Estelle Collin, Biraja Dash, Abhay Pandit, and David Eglin. "Recent Advances in Biomaterial Based Tissue Engineering for Intervertebral Disc Regeneration." In Cells and Biomaterials for Intervertebral Disc Regeneration, 43–96. Cham: Springer International Publishing, 2010. http://dx.doi.org/10.1007/978-3-031-02580-8_2.

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Lee, Y. J., I. A. Kim, S. A. Park, W. J. Shin, C. W. Kim, J. W. Bae, Ki Dong Park, and Jung Woog Shin. "A Tissue Engineering Based Approach to Regeneration of Intervertebral Disc." In Advanced Biomaterials VII, 397–400. Stafa: Trans Tech Publications Ltd., 2007. http://dx.doi.org/10.4028/0-87849-436-7.397.

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Cociug, A., V. Nacu, and O. Macagonova. "The Modality of the Regeneration of the Intervertebral Lombar Disc in Osteochondrosis." In 3rd International Conference on Nanotechnologies and Biomedical Engineering, 454–57. Singapore: Springer Singapore, 2016. http://dx.doi.org/10.1007/978-981-287-736-9_107.

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Varden, Lara J., Petra Kraus, Arthur J. Michalek, Thomas Lufkin, and Shantanu Sur. "CHAPTER 13. Peptide-based Biomaterials for Repair and Regeneration of the Intervertebral Disc." In Soft Matter Series, 429–58. Cambridge: Royal Society of Chemistry, 2020. http://dx.doi.org/10.1039/9781839161148-00429.

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Mercuri, Jeremy J., and Dan T. Simionescu. "Advances in Tissue Engineering Approaches to Treatment of Intervertebral Disc Degeneration: Cells and Polymeric Scaffolds for Nucleus Pulposus Regeneration." In Polymers in Nanomedicine, 201–31. Berlin, Heidelberg: Springer Berlin Heidelberg, 2011. http://dx.doi.org/10.1007/12_2011_149.

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Khang, Gilson, Jeong Eun Song, Nirmalya Tripathy, Eun Young Kim, and Dongwon Lee. "Recent Advances in Regenerative Approaches to Intervertebral Disc Degeneration." In Biomedical Engineering: Frontier Research and Converging Technologies, 427–44. Cham: Springer International Publishing, 2015. http://dx.doi.org/10.1007/978-3-319-21813-7_18.

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Gantenbein-Ritter, B., and D. Sakai. "Biomaterials for Intervertebral Disc Regeneration." In Comprehensive Biomaterials, 161–69. Elsevier, 2011. http://dx.doi.org/10.1016/b978-0-08-055294-1.00210-5.

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Conference papers on the topic "Intervertebral Disc Regeneration"

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Wiltsey, Craig, Thomas Christiani, Jesse Williams, Jamie Coulter, Dana Demiduke, Katelynn Toomer, Sherri English, et al. "Tissue Engineering of the Intervertebral Disc." In ASME 2012 Summer Bioengineering Conference. American Society of Mechanical Engineers, 2012. http://dx.doi.org/10.1115/sbc2012-80349.

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Tissue engineering is a rapidly growing field of research that aims to repair damaged tissues within the body. Among tissue engineering approaches is the use of scaffolds to help regenerate lost tissues. Scaffolds provide structural support for specific areas within the body, namely load bearing regions, and allow for cells to be seeded within the scaffold for tissue regeneration. Scaffolds that specifically replicate the properties and/or composition of native tissues are referred to as biomimetic scaffolds.

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Lee, Cynthia R., Mauro Alini, and James C. Iatridis. "Organ Culture System for Mechanobiology Studies of the Intervertebral Disc." In ASME 2004 International Mechanical Engineering Congress and Exposition. ASMEDC, 2004. http://dx.doi.org/10.1115/imece2004-61248.

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The development of in vitro models is critical for furthering understanding of the intervertebral disc and the development of disc regeneration/tissue engineering. An in vitro culture system targeted towards mechano-biology studies of the intervertebral disc (IVD) was built and validated using bovine coccygeal discs. Discs were maintained in culture for up to one week with and without vertebral endplates. Water content and glycosaminoglycan content were found to be stable and cells were metabolically active when cultured under a 5kg static load.

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Francisco, Aubrey T., Robert J. Mancino, Claire G. Jeong, Isaac O. Karikari, Robby D. Bowles, Stephen L. Craig, and Lori A. Setton. "Injectable and Photocrosslinkable Laminin Functionalized Biomaterials for Intervertebral Disc Regeneration." In ASME 2012 Summer Bioengineering Conference. American Society of Mechanical Engineers, 2012. http://dx.doi.org/10.1115/sbc2012-80660.

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Biological and anatomical changes of intervertebral disc (IVD) degeneration frequently occur in the nucleus pulposus (NP) [1]. Changes in NP matrix composition coincide with the loss of a distinct notochord derived cell population [2],[3], which may have the potential to generate or maintain a functional NP-like matrix. Immature NP cells reside in an environment rich in laminin and express specific laminin-binding receptors [4],[5]. Additionally, NP cells attach in higher numbers to laminins as compared to cells isolated from other regions of the IVD [6]. Our initial work demonstrated that matrix protein and stiffness modulate NP cell-cell interactions upon surfaces [7], with results that suggest soft, laminin-functionalized hydrogels may be useful for promoting an NP-like cell phenotype.

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Natarajan, Raghu N., Alejandro Espinoza, and Gunnar B. J. Andersson. "Effect of Needle Puncture Injury on Human Intervertebral Disc Mechanics." In ASME 2010 Summer Bioengineering Conference. American Society of Mechanical Engineers, 2010. http://dx.doi.org/10.1115/sbc2010-19116.

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Diagnosis, repair and regeneration of the disc often necessitate needle injection to the nucleus pulposus through the annulus. Discography in which a radio opaque material is injected into the nucleus and electrothermal treatment involving inserting a catheter into the disc requires disruption of the annulus through needle puncture. Annulus puncture may also be required during placement of nucleus implants. Needle puncture is also used to inject growth factors, gene and cell therapy for regeneration of the disc. In animal models, disc degeneration is induced over time by needle puncture of the annulus. The severity of the degeneration depends on the magnitude of the annulus needle puncture. One thing that is not clear is how much of the observed changes in the disc biomechanics and biochemical changes are due to nucleus treatment and how much is due to annular disruption through needle puncture. Animal model studies have shown that significant changes in disc mechanics were noticed within 1 week of needle puncture with a large-gauge needle. Another in-vitro animal study showed that biomechanical changes were observed in the disc when the ratio of needle diameter to disc height is greater than 40%. All these studies were focused on the effect of small number of needle diameters and addressed using animal cadaver models. How these needle puncture injury studies on small and large animal models can be extrapolated to human conditions is still not known. Thus there is need to evaluate effect of range of needle puncture diameters in human lumbar disc biomechanics. The purpose of this study is, with the help of a finite element models, quantify the biomechanical effect due to varying size of needle punctures in a human lumbar intervertebral disc.

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Houseman, C., M. Scro, S. Belverud, D. Chen, P. Razzano, M. Levine, D. A. Grande, and N. O. Chahine. "Effect of TGF-β3 on the Gene Expression of Intervertebral Disc Cells in 3D Pellet Cultures." In ASME 2010 Summer Bioengineering Conference. American Society of Mechanical Engineers, 2010. http://dx.doi.org/10.1115/sbc2010-19246.

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Intervertebral disc (IVD) degeneration typically involves changes in the multiple constitutive tissues of the IVD. Many tissue repair efforts have focused on the use of differentiated disc cells or stem cells for the regeneration of an IVD in vitro. Consequently, successful long term culture of human disc cells is pivotal for tissue regeneration of the IVD. The aim of this study is to establish a long-term in vitro culture system for the growth of disc cells that maintain their phenotype based on the anatomical origin (annulus fibrosus (AF), nucleus pulposus (NP), or the vertebral end-plates (EP)). This maintenance of phenotype is crucial for examination of treatment efficacy, which is typically designed to induce regeneration of a single tissue type (i.e. injection of growth factors into the NP or anti-inflammatory treatment of the EPs).

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Korecki, Casey L., Catherine K. Kuo, Rocky S. Tuan, and James C. Iatridis. "Effect of Age and Frequency on Intervertebral Disc Cell Response to Dynamic Compression." In ASME 2007 Summer Bioengineering Conference. American Society of Mechanical Engineers, 2007. http://dx.doi.org/10.1115/sbc2007-176595.

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The intervertebral disc (IVD) is a unique orthopaedic tissue consisting of at least two cell types: fibroblast-like annulus fibrosus (AF) cells and chondrocyte-like nucleus pulposus (NP) cells. Culture of cells in 3D gel matrices (such as alginate or agarose), maintains the normal morphology and ECM molecule production of chondrocytes for extended periods of time and also allows the application of various forms of mechanical stimulation, such as hydrostatic or compressive loading. In vivo studies have shown IVD cells to be responsive to frequency, duration, and amplitude of mechanical load [1]. IVD literature on mechanobiology uses varying methodologies to apply dynamic loads (compression, hydrostatic forces), with different times of mechanical stimulation, differences in model systems (in vivo, tissue culture, cell culture), species, and ages, and an optimal loading protocol to stimulate extracellular matrix protein accumulation is unknown. The overall goal of this work is to evaluate the potential, and perhaps even feasibility, of mechanical stimulation for extracellular matrix (ECM) regeneration using intervertebral disc cells. Also of interest is whether cells from mature tissue are capable of serving as a potential cell source for future IVD regeneration [2,3].

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Cleary, Heather, Thomas Barkley, Adam Goodman, Michael Payne, John Virtue, Jennifer Vernengo, and Jennifer Kadlowec. "Design of a Bioreactor for Mechanical Stimulation of Adipose Derived Stem Cells for Intervertebral Disc Tissue Engineering." In ASME 2012 Summer Bioengineering Conference. American Society of Mechanical Engineers, 2012. http://dx.doi.org/10.1115/sbc2012-80745.

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Lower back pain is one of the most common medical problems in the world [1], affecting between 70% and 85% of the US population at some point during their lives [2]. Disc degeneration is caused by biological changes in the disc, which result in dehydration of the nucleus pulposus (NP). The long term goal of this project is to treat disc degeneration with a tissue engineering strategy for the regeneration of the nucleus pulposus using messechymal stem cells derived from adipose tissue. It has been established in cartilage regeneration studies that cyclic compressive loading of stem cells is beneficial for tissue formation compared to static culture [3–7]. In this work, a bioreactor is being developed that can subject cell-seeded polymeric tissue engineering scaffolds to dynamic compressive forces. Ultimately, the bioreactor will be used to study the effects of different loading parameters on the production of new nucleus pulposus tissue from adipose-derived stem cells.

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Orlansky, Amy S., John I. Boxberger, and Dawn M. Elliott. "The Dynamic Viscoelastic Properties of the Rat Lumbar Disc Are Decreased Following Nucleus Pulposus GAG Reduction." In ASME 2008 Summer Bioengineering Conference. American Society of Mechanical Engineers, 2008. http://dx.doi.org/10.1115/sbc2008-192634.

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The intervertebral disc has the important biomechanical function of dissipating energy during spinal loading. With degeneration, the disc experiences, among other changes, a loss of mechanical function and degradation of its composition. Using a rat model of early disc degeneration by injection of Chondroitinase ABC (ChABC), glycosaminoglycan (GAG) content in the nucleus pulposus (NP) was reduced which altered neutral zone mechanical properties. The contribution of decreased NP GAG content to the dynamic viscoelastic properties has yet to be determined. The advantage of dynamic viscoelastic testing is that it provides both viscous and elastic stiffness values as a function of loading frequency. These methods have been employed previously in a rabbit disc regeneration model, in ligament under three modes of loading, and in NP under oscillatory shear and compression. Therefore, the objective of this study was to determine the viscoelastic behavior of a rat lumbar disc at several equilibrium strains and to quantify the impact of GAG reduction on this behavior. Our hypotheses were: 1) elastic stiffness would be greater, and viscous stiffness and loss angle would be lower with increased frequency, and 2) both elastic and viscous stiffness would be lower in the reduced GAG discs at all frequencies.

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Tasci, Arzu, Ladina Ettinger, Stephen Ferguson, and Philippe Büchler. "The Role of Agarose Mechanical Response on the Matrix Synthesis of Nucleus Pulposus Cells: A Pilot Study." In ASME 2009 Summer Bioengineering Conference. American Society of Mechanical Engineers, 2009. http://dx.doi.org/10.1115/sbc2009-206763.

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Low back pain is the most common spinal disorder and its main cause is intervertebral disc (IVD) degeneration. IVD has a major role of withstanding loads generated in the spine during daily activities. However, it has a limited capacity for self-repair. Since it has an avascular structure, the pathways it uses for regeneration is quite complex and not yet well understood. The mechanical stimulation studies on the cell seeded constructs revealed that cells regulate their biosynthetic activity with cyclic loading [1,2]. The mechanical properties of the scaffold might play an important role in the transmission of mechanical signals to the embedded cells. The objective of this study is to investigate the effect of agarose concentration on the amount of extracellular matrix synthesis in IVD cell seeded constructs under static culture and cyclic loading conditions.

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Sen, Sounok, John I. Boxberger, Yvonne Schroeder, Alejandro Espinoza Orias, and Dawn M. Elliott. "Effect of Degeneration on the Dynamic Viscoelastic Properties of Human Annulus Fibrosus in Tension." In ASME 2008 Summer Bioengineering Conference. American Society of Mechanical Engineers, 2008. http://dx.doi.org/10.1115/sbc2008-193057.

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Physiological cyclic loading of the intervertebral disc generally occurs between 1 and 5 Hz [1]. However, most mechanical assessments of disc AF tissue have relied on uniaxial tensile tests under quasi-static conditions [2]. Furthermore, the few studies that have addressed AF viscoelasticity have reported only static viscoelastic properties such as creep or stress-relaxation [3]. As such, there exists almost no data characterizing the dynamic viscoelastic properties of AF tissue in tension. Such data would be critical for several applications: to elucidate the mechanical progression of intervertebral disc degeneration, to develop and validate structural finite element models, and to provide native tissue benchmarks for regenerative approaches that aim to restore mechanical function to diseased or degenerate tissue. Therefore, the objectives of this study are to: (1) quantify human AF tissue frequency-dependent and strain-dependent viscoelastic properties of human AF tissue in circumferential tension, and (2) determine the effects of disc degeneration on these properties.

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