Artículos de revistas: "Intervertebral Disc Regeneration"

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Ju, Derek G., Linda E. Kanim y Hyun W. Bae. "Intervertebral Disc Repair: Current Concepts". Global Spine Journal 10, n.º 2_suppl (abril de 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. y 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, n.º 4 (20 de julio de 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 y Yuling Li. "Applications of Functionalized Hydrogels in the Regeneration of the Intervertebral Disc". BioMed Research International 2021 (19 de agosto de 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 y N. G. Chopik. "BIOCHEMICAL AND BIOMECHANICAL SUBSTANTIATION OF REPARATIVE REGENERATION OF INTERVERTEBRAL DISCS IN PATIENTS WITH DEGENERATIVE DISC DISEASES". Eastern Ukrainian Medical Journal 8, n.º 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 y Mick J. Perez-Cruet. "In vivo intervertebral disc regeneration using stem cell–derived chondroprogenitors". Journal of Neurosurgery: Spine 10, n.º 3 (marzo de 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, n.º 8 (31 de agosto de 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 y Isaac L. Moss. "Hydrogel-Based Strategies for Intervertebral Disc Regeneration: Advances, Challenges and Clinical Prospects". Gels 10, n.º 1 (15 de enero de 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 y 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, n.º 03 (julio de 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 (23 de abril de 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 y J. Caldeira. "Intervertebral disc decellularisation: progress and challenges". European Cells and Materials 42 (6 de octubre de 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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Du, Yuxiang, Zhikun Wang, Yangming Wu, Chengyi Liu y Lingli Zhang. "Intervertebral Disc Stem/Progenitor Cells: A Promising “Seed” for Intervertebral Disc Regeneration". Stem Cells International 2021 (28 de julio de 2021): 1–12. http://dx.doi.org/10.1155/2021/2130727.

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Intervertebral disc (IVD) degeneration is considered to be the primary reason for low back pain (LBP), which has become more prevalent from 21 century, causing an enormous economic burden for society. However, in spite of remarkable improvements in the basic research of IVD degeneration (IVDD), the effects of clinical treatments of IVDD are still leaving much to be desired. Accumulating evidence has proposed the existence of endogenous stem/progenitor cells in the IVD that possess the ability of proliferation and differentiation. However, few studies have reported the biological properties and potential application of IVD progenitor cells in detail. Even so, these stem/progenitor cells have been consumed as a promising cell source for the regeneration of damaged IVD. In this review, we will first introduce IVD, describe its physiology and stem/progenitor cell niche, and characterize IVDSPCs between homeostasis and IVD degeneration. We will then summarize recent studies on endogenous IVDSPC-based IVD regeneration and exogenous cell-based therapy for IVDD. Finally, we will discuss the potential applications and future developments of IVDSPC-based repair of IVD degeneration.

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SAKAI, Daisuke. "Intervertebral disc regeneration from cellular level". Journal of Japanese Society of Lumbar Spine Disorders 15, n.º 1 (2009): 95–98. http://dx.doi.org/10.3753/yotsu.15.95.

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Fiordalisi, Morena, Ana João Silva, Mário Barbosa, Raquel Gonçalves y Joana Caldeira. "Decellularized Scaffolds for Intervertebral Disc Regeneration". Trends in Biotechnology 38, n.º 9 (septiembre de 2020): 947–51. http://dx.doi.org/10.1016/j.tibtech.2020.05.002.

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Deml, Moritz C., Lorin M. Benneker, Tanja Schmid, Daisuke Sakai, Christoph E. Albers, Sven Hoppe y Stephan Zeiter. "Ventral Surgical Approach for an Intervertebral Disc Degeneration and Regeneration Model in Sheep Cervical Spine: Anatomic Technical Description, Strengths and Limitations". Veterinary and Comparative Orthopaedics and Traumatology 32, n.º 05 (3 de junio de 2019): 389–93. http://dx.doi.org/10.1055/s-0039-1688988.

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Abstract Objective Sheep are used as a large animal model for intervertebral disc research. However, for the ovine ventral surgical approach to the cervical disc, limited descriptions exist. We, therefore, give a detailed in vivo anatomical description of this approach in sheep for the use in intervertebral disc regeneration and degeneration models to increase the reproducibility of such interventions. Materials and Methods Eighteen female Swiss white alpine sheep, with an age range of 2 to 4 years, were used. A ventral surgical access was performed to establish defined intervertebral disc punch defect from cervical levels C3/4 to C5/6. Cervical levels C2/3 and C6/7 were used as negative controls. Intraoperative findings, radiographical controls and postoperative clinical follow-up were documented and collected for this clinical report. Results All sheep recovered rapidly from the surgical intervention. Two sheep developed wound seroma, which resorbed spontaneously. Two further sheep showed wound dehiscence within 3 days after surgery, which had to be revised. No clinical wound infections occurred and all sheep healed well and did not show any side effects related to the surgical procedure. Conclusion The ventral surgical access to the ovine cervical spine is a safe and reliable procedure. The advantage of the cervical intervertebral disc is the easier surgical access and the increased disc height compared to the sheep lumbar spine. Since the ovine cervical intervertebral disc shows a high grade of similarities (e.g. molecular characteristics) compared to human discs, it is a promising degeneration and regeneration model for disc diseases.

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Jahr, H. "ANATOMY AND MICROENVIRONMENT OF THE INTERVERTEBRAL DISC". Orthopaedic Proceedings 106-B, SUPP_1 (2 de enero de 2024): 100. http://dx.doi.org/10.1302/1358-992x.2024.1.100.

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Degeneration of the intervertebral disc (IVD), and subsequent low back pain, is an almost inevitable cause of disability. The underlying mechanisms are complex and current therapeutic strategies mainly focus on symptomatic relief rather than on the intrinsic regeneration of the IVD. This talk will provide an overview of special anatomical features and the composition of the IVD as well as its cellular microenvironment. Selected promising conceptional regenerative approaches will be discussed.

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Cheng, Yunzhong, Honghao Yang, Yong Hai y Yuzeng Liu. "Researches on Stem and Progenitor Cells in Intervertebral Discs: An Analysis of the Scientific Landscape". Stem Cells International 2022 (1 de septiembre de 2022): 1–17. http://dx.doi.org/10.1155/2022/1274580.

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Low back pain (LBP) is a common clinical symptom, and the prevalence is ranged from 60% to 70%. With the deepening of basic research, the development of intervertebral disc regeneration-oriented cell therapy, especially stem and progenitor cells therapy, showed good research prospects and was expected to become new methods of treatment for LBP. Our study is aimed at analyzing the scientific output of stem and progenitor cells in intervertebral discs and at driving future research into new publications. Researches focused on this file were searched from the Science Citation Index Expanded (SCI-E) of the Web of Science (WOS) core collection database and were screened according to inclusion criteria. We evaluated and visualized the results, including annual publications, citations, authors, organizations, countries, research directions, funds, and journals by bibliometric website, VOSviewer, and Citespace softwares on May 27, 2022. A total of 450 original articles and reviews were included, and the overall trend of the number of publications rapidly increased. In worldwide, China and the USA were the leading countries for research production. The retrieved 450 publications received 14322 citations, with an average of 31.83 citations and an H-index of 62. The most high-yield author, organization, country, research directions, funds, and journals were Chen QX from Zhejiang University, Zhejiang University, China, Cell Biology, National Natural Science Foundation of China, and Spine, respectively. Keywords cluster analysis showed the research hotspots in the future, including “human intervertebral disc”, “adipose-derived mesenchymal stem cell”, “intervertebral disc degeneration”, “degenerative disc model”, “nucleus pulposus regeneration”, “human cartilage”, “3d culture”, “shrinkage-free preparation”, and “polylactide disc”. Furthermore, with accumulating evidence demonstrating the role of stem and progenitor cells in intervertebral discs, “microenvironment”, “activation”, “intervertebral disc degeneration”, and “oxidative stress” are becoming the research frontiers and trends.

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Molinos, Maria, Catarina R. Almeida, Joana Caldeira, Carla Cunha, Raquel M. Gonçalves y Mário A. Barbosa. "Inflammation in intervertebral disc degeneration and regeneration". Journal of The Royal Society Interface 12, n.º 104 (marzo de 2015): 20141191. http://dx.doi.org/10.1098/rsif.2014.1191.

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Intervertebral disc (IVD) degeneration is one of the major causes of low back pain, a problem with a heavy economic burden, which has been increasing in prevalence as populations age. Deeper knowledge of the complex spatial and temporal orchestration of cellular interactions and extracellular matrix remodelling is critical to improve current IVD therapies, which have so far proved unsatisfactory. Inflammation has been correlated with degenerative disc disease but its role in discogenic pain and hernia regression remains controversial. The inflammatory response may be involved in the onset of disease, but it is also crucial in maintaining tissue homeostasis. Furthermore, if properly balanced it may contribute to tissue repair/regeneration as has already been demonstrated in other tissues. In this review, we focus on how inflammation has been associated with IVD degeneration by describing observational and in vitro studies as well as in vivo animal models. Finally, we provide an overview of IVD regenerative therapies that target key inflammatory players.

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Oehme, David, Tony Goldschlager, Peter Ghosh, Jeffrey V. Rosenfeld y Graham Jenkin. "Cell-Based Therapies Used to Treat Lumbar Degenerative Disc Disease: A Systematic Review of Animal Studies and Human Clinical Trials". Stem Cells International 2015 (2015): 1–16. http://dx.doi.org/10.1155/2015/946031.

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Low back pain and degenerative disc disease are a significant cause of pain and disability worldwide. Advances in regenerative medicine and cell-based therapies, particularly the transplantation of mesenchymal stem cells and intervertebral disc chondrocytes, have led to the publication of numerous studies and clinical trials utilising these biological therapies to treat degenerative spinal conditions, often reporting favourable outcomes. Stem cell mediated disc regeneration may bridge the gap between the two current alternatives for patients with low back pain, often inadequate pain management at one end and invasive surgery at the other. Through cartilage formation and disc regeneration or via modification of pain pathways stem cells are well suited to enhance spinal surgery practice. This paper will systematically review the current status of basic science studies, preclinical and clinical trials utilising cell-based therapies to repair the degenerate intervertebral disc. The mechanism of action of transplanted cells, as well as the limitations of published studies, will be discussed.

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Hu, Binwu, Ruijun He, Kaige Ma, Zhe Wang, Min Cui, Hongzhi Hu, Saroj Rai, Baichuan Wang y Zengwu Shao. "Intervertebral Disc-Derived Stem/Progenitor Cells as a Promising Cell Source for Intervertebral Disc Regeneration". Stem Cells International 2018 (18 de diciembre de 2018): 1–11. http://dx.doi.org/10.1155/2018/7412304.

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Intervertebral disc (IVD) degeneration is considered to be the primary reason for low back pain. Despite remarkable improvements in both pharmacological and surgical management of IVD degeneration (IVDD), therapeutic effects are still unsatisfactory. It is because of the fact that these therapies are mainly focused on alleviating the symptoms rather than treating the underlying cause or restoring the structure and biomechanical function of the IVD. Accumulating evidence has revealed that the endogenous stem/progenitor cells exist in the IVD, and these cells might be a promising cell source in the regeneration of degenerated IVD. However, the biological characteristics and potential application of IVD-derived stem/progenitor cells (IVDSCs) have yet to be investigated in detail. In this review, the authors aim to perform a review to systematically discuss (1) the isolation, surface markers, classification, and biological characteristics of IVDSCs; (2) the aging- and degeneration-related changes of IVDSCs and the influences of IVD microenvironment on IVDSCs; and (3) the potential for IVDSCs to promote regeneration of degenerated IVD. The authors believe that this review exclusively address the current understanding of IVDSCs and provide a novel approach for the IVD regeneration.

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Jandial, Rahul, Henry E. Aryan, John Park, William T. Taylor y Evan Y. Snyder. "Stem cell–mediated regeneration of the intervertebral disc: cellular and molecular challenges". Neurosurgical Focus 24, n.º 3-4 (marzo de 2008): E21. http://dx.doi.org/10.3171/foc/2008/24/3-4/e20.

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✓ Regenerative medicine and stem cells hold great promise for intervertebral disc (IVD) disease. The therapeutic implications of utilizing stem cells to repair degenerated discs and treat back pain are highly anticipated by both the clinical and scientific communities. Although the avascular environment of the IVD poses a challenge for stem cell–mediated regeneration, neuroprogenitor cells have been discovered within degenerated discs, allowing scientists to revisit the hostile environment of the IVD as a target for stem cell therapy. Issues now under investigation include the timing of cell delivery and manipulation of stem cells to make them more efficient and adaptive in the IVD niche. This review covers the mechanisms underlying disc degeneration as well as the molecular and cellular challenges involved in directing stem cells to the desired cell type for intradiscal transplantation.

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Freimark, Denise y Peter Czermak. "Cell-Based Regeneration of Intervertebral Disc Defects: Review and Concepts". International Journal of Artificial Organs 32, n.º 4 (abril de 2009): 197–203. http://dx.doi.org/10.1177/039139880903200403.

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During the last century low back pain has emerged as a widespread disease often caused by intervertebral disc degeneration (IDD). IDD is a complex problem in which a variety of causes play a role. As IDD causes high costs, corporate interest has led to a number of therapies being developed. Today, these therapies focus not only on minimizing the pain caused by this disease but also on restoring intervertebral disc function. These approaches are often biological and aim to stimulate the regeneration of the intervertebral disc by injection of activator proteins, biomaterials, different cell types or complex cell matrix composites. Genetic engineering of disc cells and in vitro tissue engineering also offer a possibility for curing IDD. This article gives an overview of these concepts.

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Bill, Tawil y Kelly Tamura. "Degenerative disc disease: analysis of treatments, tissue, and market". Advances in Tissue Engineering & Regenerative Medicine: Open Access 10, n.º 1 (16 de enero de 2024): 1–7. http://dx.doi.org/10.15406/atroa.2024.10.00145.

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The prevalence of intervertebral thinning discs and the degradation of spinal discs as a whole has created a new market and area of research to find a solution to this age-related problem. The loss of the cartilage cushioning two vertebrae is called degenerative disc disease, or DDD. DDD can impact a patient’s quality of life greatly – putting them in severe pain, limiting mobility, and decreasing their ability to perform daily activities. The market for DDD treatment shows promising growth, both globally and in the US. Most of the drugs and devices that are currently on the market aim to alleviate pain or reduce inflammation, addressing the symptoms of DDD rather than regenerating the lost disc tissue. However, there are many new treatments that are in development or are being tested in clinical trials that could satisfy this need. In the context of tissue engineering, regeneration of the intervertebral disc is a prime target. A scaffold could fulfill the need for mechanical support in between the vertebrae and growth factors and cells could stimulate the regrowth of the injured tissue.

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Vadalà, Gianluca, Fabrizio Russo, Luca Ambrosio, Mattia Loppini y Vincenzo Denaro. "Stem cells sources for intervertebral disc regeneration". World Journal of Stem Cells 8, n.º 5 (2016): 185. http://dx.doi.org/10.4252/wjsc.v8.i5.185.

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Molinos, Mário, Catarina R. Almeida, Joana Caldeira, Carla Cunha, Raquel M. Gonçalves y Mário A. Barbosa. "Inflammation in intervertebral disc degeneration and regeneration". Journal of The Royal Society Interface 12, n.º 108 (julio de 2015): 20150429. http://dx.doi.org/10.1098/rsif.2015.0429.

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Grad, Sibylle, Mauro Alini, David Eglin, Daisuke Sakai, Joji Mochida, Sunil Mahor, Estelle Collin, Biraja Dash y Abhay Pandit. "Cells and Biomaterials for Intervertebral Disc Regeneration". Synthesis Lectures on Tissue Engineering 2, n.º 1 (enero de 2010): 1–104. http://dx.doi.org/10.2200/s00250ed1v01y201006tis005.

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Kalson, NS, S. Richardson y JA Hoyland. "Strategies for regeneration of the intervertebral disc". Regenerative Medicine 3, n.º 5 (septiembre de 2008): 717–29. http://dx.doi.org/10.2217/17460751.3.5.717.

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Bowles, Robert D. y Lori A. Setton. "Biomaterials for intervertebral disc regeneration and repair". Biomaterials 129 (junio de 2017): 54–67. http://dx.doi.org/10.1016/j.biomaterials.2017.03.013.

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Gantenbein, B. "DEVELOPING REGENERATION THERAPIES FOR THE INTERVERTEBRAL DISC". Orthopaedic Proceedings 106-B, SUPP_2 (2 de enero de 2024): 49. http://dx.doi.org/10.1302/1358-992x.2024.2.049.

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Stem cell therapy for the intervertebral disc (IVD) is highly debated but holds great promises. From previous studies, it is known that notochordal cells are highly regenerative and may stimulate other differentiated cells to produce more matrix. Lately, a particular tissue-specific progenitor cell population has been identified in the centre of the intervertebral disc (IVD. The current hope is that these nucleus pulposus progenitor cells (NPPC) could play a particular role in IVD regeneration.Current evidence confirms the presence of these cells in murine, canine, bovine and in the human fetal/surgical samples. Noteworthy, one of the main markers to identify these cells, i.e., Tie2, is a typical marker for endothelial cells. Thus, it is not very clear what their origin and their role might be in the context of developmental biology. In human surgical specimens, their presence is, even more, obscured depending on the donor's age and the condition of the IVD and other yet unknown factors.Here, I revisit the recent literature on regenerative cells identified for the IVD in the past decades. Current evidence how these NPPC can be isolated and detected in various species and tissues will be recapitulated. Future directions will be provided on how these progenitor cells could be used for regenerative medicine and tissue engineering.

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PELETTI-FIGUEIRÓ, MANUELA, ISRAEL SILVEIRA DE AGUIAR, SUELEN PAESI, DENISE CANTARELLI MACHADO, SERGIO ECHEVERRIGARAY, MARIANA ROESCH-ELY, ASDRUBAL FALAVIGNA y JOÃO ANTONIO PÊGAS HENRIQUES. "HISTOLOGICAL MARKERS OF DEGENERATION AND REGENERATION OF THE HUMAN INTERVERTEBRAL DISK". Coluna/Columna 16, n.º 1 (enero de 2017): 42–47. http://dx.doi.org/10.1590/s1808-185120171601170833.

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ABSTRACT Objective: To define histological scores for intervertebral disc degeneration that would enable the definition of morphological characteristics of disease, besides improving knowledge of the lumbar degenerative disc disease by means of immunohistochemical markers. Methods: Hematoxylin and Eosin, Alcian/PAS, Masson Trichrome and Safranin O/FCF staining was used on the intervertebral disc degeneration sections of patients with lumbar degenerative disc disease. The protein markers defined in immunohistochemistry were cell proliferation (Ki-67) and apoptosis (p53). Results: The study data enabled the determination of Safranin O/FCF stain as the most effective one for evaluating parameters such as area, diameter, and number of chondrocyte clusters. The importance of using stains in association, such as Safranin O/FCF, Masson Trichrome, Alcian/PAS and Hematoxylin and Eosin, was also determined, as they are complementary for the histopathological verification of intervertebral disc degeneration. By expressing proteins using the immunohistochemistry technique, it was possible to consider two stages of disc degeneration: cell proliferation with chondrocyte cluster formation, and induction of apoptosis. Conclusion: This study enabled the histological and immunohistochemical characterization to be determined for lumbar degenerative disc disease, and its degrees of evolution, by determining new disc degeneration scores.

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Doench, Ingo, Tuan Tran, Laurent David, Alexandra Montembault, Eric Viguier, Christian Gorzelanny, Guillaume Sudre et al. "Cellulose Nanofiber-Reinforced Chitosan Hydrogel Composites for Intervertebral Disc Tissue Repair". Biomimetics 4, n.º 1 (20 de febrero de 2019): 19. http://dx.doi.org/10.3390/biomimetics4010019.

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The development of non-cellularized composites of chitosan (CHI) hydrogels, filled with cellulose nanofibers (CNFs) of the type nanofibrillated cellulose, was proposed for the repair and regeneration of the intervertebral disc (IVD) annulus fibrosus (AF) tissue. With the achievement of CNF-filled CHI hydrogels, biomaterial-based implants were designed to restore damaged/degenerated discs. The structural, mechanical and biological properties of the developed hydrogel composites were investigated. The neutralization of weakly acidic aqueous CNF/CHI viscous suspensions in NaOH yielded composites of physical hydrogels in which the cellulose nanofibers reinforced the CHI matrix, as investigated by means of microtensile testing under controlled humidity. We assessed the suitability of the achieved biomaterials for intervertebral disc tissue engineering in ex vivo experiments using spine pig models. Cellulose nanofiber-filled chitosan hydrogels can be used as implants in AF tissue defects to restore IVD biomechanics and constitute contention patches against disc nucleus protrusion while serving as support for IVD regeneration.

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Crevensten, Gwen, Andrew J. L. Walsh, Dheera Ananthakrishnan, Paul Page, George M. Wahba, Jeffrey C. Lotz y Sigurd Berven. "Intervertebral Disc Cell Therapy for Regeneration: Mesenchymal Stem Cell Implantation in Rat Intervertebral Discs". Annals of Biomedical Engineering 32, n.º 3 (marzo de 2004): 430–34. http://dx.doi.org/10.1023/b:abme.0000017545.84833.7c.

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32

Moon, Seong-Hwan. "Biochemical Factors of Intervertebral Disc Degeneration: Implications for Disc Regeneration". Journal of Korean Society of Spine Surgery 14, n.º 2 (2007): 120. http://dx.doi.org/10.4184/jkss.2007.14.2.120.

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33

Lee, Y. J., I. A. Kim, S. A. Park, W. J. Shin, C. W. Kim, J. W. Bae, Ki Dong Park y Jung Woog Shin. "A Tissue Engineering Based Approach to Regeneration of Intervertebral Disc". Key Engineering Materials 342-343 (julio de 2007): 397–400. http://dx.doi.org/10.4028/www.scientific.net/kem.342-343.397.

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Thermosensitive scaffold was suggested for the partial replacement of nucleus in degenerated intervertebral disc with a minimally invasive surgical procedure. Biocompatible and thermosensitive scaffolds were prepared by coupling reaction of Pluronic with chitosan and it was inserted in degenerative spinal motion segments. To confirm the regeneration of degenerative discs and subsequent structural stability, cell proliferation and morphological changes were evaluated using relaxation time, quantity of DNA and histological examination. As a result, inserted group showed higher relaxation time, reduced the decrement of DNA contents, and accumulated GAG amount. The results confirmed the potential of thermosensitive scaffolds and minimally invasive surgical procedure for the regeneration of degenerative discs.

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Xia, Kaishun, Jian Zhu, Jianming Hua, Zhe Gong, Chao Yu, Xiaopeng Zhou, Jingkai Wang et al. "Intradiscal Injection of Induced Pluripotent Stem Cell-Derived Nucleus Pulposus-Like Cell-Seeded Polymeric Microspheres Promotes Rat Disc Regeneration". Stem Cells International 2019 (2 de mayo de 2019): 1–14. http://dx.doi.org/10.1155/2019/6806540.

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Background. Cell replacement therapy is an attractive alternative for treating degenerated intervertebral discs (IVDs), which are related to the reduction of nucleus pulposus-like cells (NP-lCs) and the loss of the extracellular matrix. Induced pluripotent stem cells (iPSCs) which resemble embryonic stem cells are considered to be a potential resource for restoring NP-lCs and disc homeostasis. Here, we proposed an efficient two-step differentiation protocol of human iPSCs into NP-lCs and continuously tested their in vivo ability to regenerate IVDs. Methods. A polymeric gelatin microsphere (GM) was generated for sustained release of growth and differentiation factor-5 (GDF-5) and as a cell delivery vehicle of NP-lCs. By injecting NP-lC-seeded GDF-5-loaded GMs into the rat coccygeal intervertebral discs, the disc height and water content were examined with the molybdenum target radiographic imaging test and magnetic resonance imaging examination. Histology and immunohistochemistry results were shown with H&E, S-O-Fast Green, and immunohistochemistry staining. Results. We demonstrated that the injection of NP-lC-seeded GDF-5-loaded GMs could reverse IDD in a rat model. The imaging examination indicated that disc height recovered and water content increased. Histology and immunohistochemistry results indicated that the NP cells as well as their extracellular matrix were partially restored. Conclusions. The results suggest that NP-lC-seeded GDF-5-loaded GMs could partially regenerate degenerated intervertebral discs after transplantation into rat coccygeal intervertebral discs. Our study will help develop a promising method of stem cell-based therapy for IDD.

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Ashinsky, B., HE Smith, RL Mauck y SE Gullbrand. "Intervertebral disc degeneration and regeneration: a motion segment perspective". European Cells and Materials 41 (24 de marzo de 2021): 370–87. http://dx.doi.org/10.22203/ecm.v041a24.

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Back and neck pain have become primary reasons for disability and healthcare spending globally. While the causes of back pain are multifactorial, intervertebral disc degeneration is frequently cited as a primary source of pain. The annulus fibrosus (AF) and nucleus pulposus (NP) subcomponents of the disc are common targets for regenerative therapeutics. However, disc degeneration is also associated with degenerative changes to adjacent spinal tissues, and successful regenerative therapies will likely need to consider and address the pathology of adjacent spinal structures beyond solely the disc subcomponents. This review summarises the current state of knowledge in the field regarding associations between back pain, disc degeneration, and degeneration of the cartilaginous and bony endplates, the AF-vertebral body interface, the facet joints and spinal muscles, in addition to a discussion of regenerative strategies for treating pain and degeneration from a whole motion segment perspective.

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Wang, Jingkai, Yiqing Tao, Xiaopeng Zhou, Hao Li, Chengzhen Liang, Fangcai Li y Qi-xin Chen. "The potential of chondrogenic pre-differentiation of adipose-derived mesenchymal stem cells for regeneration in harsh nucleus pulposus microenvironment". Experimental Biology and Medicine 241, n.º 18 (19 de agosto de 2016): 2104–11. http://dx.doi.org/10.1177/1535370216662362.

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Recent studies indicated that cell-based therapy could be a promising approach to treat intervertebral disc degeneration. Though the harsh microenvironment in disc is still challenging to implanted cells, it could be overcome by pre-conditioning graft cells before transplantation, suggested by previous literatures. Therefore, we designed this study to identify the potential effect of chondrogenic pre-differentiation on adipose-derived mesenchymal stem cells in intervertebral disc-like microenvironment, characterized by limited nutrition, acidic, and high osmosis in vitro. Adipose-derived mesenchymal stem cells of rat were divided into five groups, embedded in type II collagen scaffold, and cultured in chondrogenic differentiation medium for 0, 3, 7, 10, and 14 days. Then, the adipose-derived mesenchymal stem cells were implanted and cultured in intervertebral disc-like condition. The proliferation and differentiation of adipose-derived mesenchymal stem cells were evaluated by cell counting kit-8 test, real-time quantitative polymerase chain reaction, and Western blotting and immunofluorescence analysis. Analyzed by the first week in intervertebral disc-like condition, the results showed relatively greater proliferative capability and extracellular matrix synthesis ability of the adipose-derived mesenchymal stem cells pre-differentiated for 7 and 10 days than the control. We concluded that pre-differentiation of rat adipose-derived mesenchymal stem cells in chondrogenic culture medium for 7 to 10 days could promote the regeneration effect of adipose-derived mesenchymal stem cells in intervertebral disc-like condition, and the pre-differentiated cells could be a promising cell source for disc regeneration medicine.

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Kibble, Matthew J., Marco Domingos, Judith A. Hoyland y Stephen M. Richardson. "Importance of Matrix Cues on Intervertebral Disc Development, Degeneration, and Regeneration". International Journal of Molecular Sciences 23, n.º 13 (21 de junio de 2022): 6915. http://dx.doi.org/10.3390/ijms23136915.

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Back pain is one of the leading causes of disability worldwide and is frequently caused by degeneration of the intervertebral discs. The discs’ development, homeostasis, and degeneration are driven by a complex series of biochemical and physical extracellular matrix cues produced by and transmitted to native cells. Thus, understanding the roles of different cues is essential for designing effective cellular and regenerative therapies. Omics technologies have helped identify many new matrix cues; however, comparatively few matrix molecules have thus far been incorporated into tissue engineered models. These include collagen type I and type II, laminins, glycosaminoglycans, and their biomimetic analogues. Modern biofabrication techniques, such as 3D bioprinting, are also enabling the spatial patterning of matrix molecules and growth factors to direct regional effects. These techniques should now be applied to biochemically, physically, and structurally relevant disc models incorporating disc and stem cells to investigate the drivers of healthy cell phenotype and differentiation. Such research will inform the development of efficacious regenerative therapies and improved clinical outcomes.

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Shen, Bojiang. "Hyaluronan: its potential application in intervertebral disc regeneration". Orthopedic Research and Reviews Volume 2 (marzo de 2010): 17–26. http://dx.doi.org/10.2147/orr.s7741.

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Huang, Shishu, Vivian Tam, Kenneth M.C. Cheung, Dan Long, Minmin Lv, Ting Wang y Guangqian Zhou. "Stem Cell-Based Approaches for Intervertebral Disc Regeneration". Current Stem Cell Research & Therapy 6, n.º 4 (1 de diciembre de 2011): 317–26. http://dx.doi.org/10.2174/157488811797904335.

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40

Hall, Ronald A., Ezequiel H. Cassinelli y James D. Kang. "Degeneration, repair, and regeneration of the intervertebral disc". Current Opinion in Orthopedics 11, n.º 5 (octubre de 2000): 413–20. http://dx.doi.org/10.1097/00001433-200010000-00014.

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Tremblay-Gravel, Julien, Derek Rosenzweig, Eric Carelli, Peter Jarzem, Thomas Steffen y Lisbet Haglund. "Tissue Engineering for Intervertebral Disc Repair and Regeneration". Global Spine Journal 5, n.º 1_suppl (mayo de 2015): s—0035–1554148—s—0035–1554148. http://dx.doi.org/10.1055/s-0035-1554148.

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42

Whatley, Benjamin R. y Xuejun Wen. "Intervertebral disc (IVD): Structure, degeneration, repair and regeneration". Materials Science and Engineering: C 32, n.º 2 (marzo de 2012): 61–77. http://dx.doi.org/10.1016/j.msec.2011.10.011.

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Migliorini, Filippo, Björn Rath, Markus Tingart, Alice Baroncini, Valentin Quack y Jörg Eschweiler. "Autogenic mesenchymal stem cells for intervertebral disc regeneration". International Orthopaedics 43, n.º 4 (10 de noviembre de 2018): 1027–36. http://dx.doi.org/10.1007/s00264-018-4218-y.

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44

Huang, Yong-Can, Jill P. G. Urban y Keith D. K. Luk. "Intervertebral disc regeneration: do nutrients lead the way?" Nature Reviews Rheumatology 10, n.º 9 (10 de junio de 2014): 561–66. http://dx.doi.org/10.1038/nrrheum.2014.91.

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Friedmann, Andrea, Andre Baertel, Christine Schmitt, Christopher Ludtka, Javorina Milosevic, Hans-Joerg Meisel, Felix Goehre y Stefan Schwan. "Intervertebral Disc Regeneration Injection of a Cell-Loaded Collagen Hydrogel in a Sheep Model". International Journal of Molecular Sciences 22, n.º 8 (19 de abril de 2021): 4248. http://dx.doi.org/10.3390/ijms22084248.

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Degenerated intervertebral discs (IVDs) were treated with autologous adipose-derived stem cells (ASC) loaded into an injectable collagen scaffold in a sheep model to investigate the implant’s therapeutic potential regarding the progression of degeneration of previously damaged discs. In this study, 18 merino sheep were subjected to a 3-step minimally invasive injury and treatment model, which consisted of surgically induced disc degeneration, treatment of IVDs with an ASC-loaded collagen hydrogel 6 weeks post-operatively, and assessment of the implant’s influence on degenerative tissue changes after 6 and 12 months of grazing. Autologous ASCs were extracted from subcutaneous adipose tissue and cultivated in vitro. At the end of the experiment, disc heights were determined by µ-CT measurements and morphological tissue changes were histologically examined.Histological investigations show that, after treatment with the ASC-loaded collagen hydrogel implant, degeneration-specific features were observed less frequently. Quantitative studies of the degree of degeneration did not demonstrate a significant influence on potential tissue regeneration with treatment. Regarding disc height analysis, at both 6 and 12 months after treatment with the ASC-loaded collagen hydrogel implant a stabilization of the disc height can be seen. A complete restoration of the intervertebral disc heights however could not be achieved.The reported injection procedure describes in a preclinical model a translational therapeutic approach for degenerative disc diseases based on adipose-derived stem cells in a collagen hydrogel scaffold. Further investigations are planned with the use of a different injectable scaffold material using the same test model.

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46

Yamada, Katsuhisa, Norimasa Iwasaki y Hideki Sudo. "Biomaterials and Cell-Based Regenerative Therapies for Intervertebral Disc Degeneration with a Focus on Biological and Biomechanical Functional Repair: Targeting Treatments for Disc Herniation". Cells 11, n.º 4 (9 de febrero de 2022): 602. http://dx.doi.org/10.3390/cells11040602.

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Intervertebral disc (IVD) degeneration is a common cause of low back pain and most spinal disorders. As IVD degeneration is a major obstacle to the healthy life of so many individuals, it is a major issue that needs to be overcome. Currently, there is no clinical treatment for the regeneration of degenerated IVDs. However, recent advances in regenerative medicine and tissue engineering suggest the potential of cell-based and/or biomaterial-based IVD regeneration therapies. These treatments may be indicated for patients with IVDs in the intermediate degenerative stage, a point where the number of viable cells decreases, and the structural integrity of the disc begins to collapse. However, there are many biological, biomechanical, and clinical challenges that must be overcome before the clinical application of these IVD regeneration therapies can be realized. This review summarizes the basic research and clinical trials literature on cell-based and biomaterial-based IVD regenerative therapies and outlines the important role of these strategies in regenerative treatment for IVD degenerative diseases, especially disc herniation.

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47

Milheiro, C., R. M. Gonçalves, M. Amendola, M. Barbosa y J. Caldeira. "CELL-DERIVED EXTRACELLULAR MATRIX TAILORING FOR INTERVERTEBRAL DISC REGENERATION". Orthopaedic Proceedings 106-B, SUPP_2 (2 de enero de 2024): 115. http://dx.doi.org/10.1302/1358-992x.2024.2.115.

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Intervertebral disc (IVD) degeneration is characterized by tissue loss of function and major structural changes, which can lead to Low Back Pain. Current treatments fail to tackle the disc's hindered function and degenerative alterations. Our goal is to promote IVD regeneration, through the recapitulation of a fetal-like microenvironment based on a tailored cell-derived matrix (CDM), rich in two fetal exclusive collagens – COLXII and COLXIV. We hypothesize that this engineered CDM will have a pro-regenerative potential and allow IVD functional restoration. Immortalized mesenchymal stromal/stem cells (iMSCs) were transduced with the CRISPR/dCas9-VP64 lentiviral system, targeting COL12A1 or COL14A1. Gene and protein expression were evaluated by qRT-PCR, Western Blot and immunofluorescence. Simultaneously, optimization of CDM decellularization protocol was performed. Process efficacy was validated by immunofluorescence. DNA content was quantified using the Quant-iT™ PicoGreen™ Kit. Successful iMSCs engineering was confirmed by an average increase of mRNA relative expression for both collagens (2.12-fold for COL12A1 and 11.7-fold for COL14A1). Protein level assessment by western blot and immunofluorescence confirmed increased COLXII and COLXIV. Decellularized CDM production was optimized. Cell removal was demonstrated by nuclear and actin staining reduction, when compared with the non-decellularized control. DNA content showed a marked decrease in both NH4OH- and SDS-based protocols. Matrix preservation after decellularization was confirmed by fibronectin staining only in the NH4OH-based decellularization. Preliminary proteomic characterization data of engineered iMSCs as shown some functional impact namely on Sonic Hedgehog (Shh) pathway and repression of pain by DREAM (Downstream regulator element antagonist modulator). In conclusion, we were able to establish a CRISPR activating system for COL12A1 and COL14A1, allowing the use of iMSCs as biofactories for a IVD fetal-tailored CDM. The use of a customized ECM and fetal microenvironment recapitulations is an innovative strategy for IVD functional restoration, and its versatility opens new avenues in the tissue regeneration field.

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48

Nakayama, Enshi, Taro Matsumoto, Tomohiko Kazama, Koichiro Kano y Yasuaki Tokuhashi. "Transplantation of dedifferentiation fat cells promotes intervertebral disc regeneration in a rat intervertebral disc degeneration model". Biochemical and Biophysical Research Communications 493, n.º 2 (noviembre de 2017): 1004–9. http://dx.doi.org/10.1016/j.bbrc.2017.09.101.

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Simonetti, L. y C. Barbara. "Reflections on the Nucleus Pulposus". Rivista di Neuroradiologia 11, n.º 3 (junio de 1998): 399–402. http://dx.doi.org/10.1177/197140099801100325.

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The intervertebral disc is usually divided into two parts, the anulus fibrosus and the nucleus pulposus. However, they are not considered two separate anatomic parts since one is essentially part of the other and this should be borne in mind to understand the process of ageing. The intervertebral disc should therefore be thought of as a dynamically evolving anatomo-functional unit. The dynamics of this process were investigated by studying the histobiochemistry of the acellular matrix of the joint cartilage in general and that of the intervertebral disc in particular to understand the effects of this arrangement on the stuctural changes to the disc induced by biomechanical stress, especially during ageing. Lastly, we focussed on the disc's nutritional mechanisms in order to examine “disc degeneration” as a sign of metabolic impairment of the nucleus pulposus and “disc regeneration”. This concept was unknown until recently and is currently monitored in percutaneous controls following treatment for disc disease.

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50

Campos, Marcelo Ferraz, Mariane de Barros Ribeiro da Silva, Maria Aparecida Silva Pinhal, Thiago Salati, Luciano Miller Reis Rodrigues y Carina Mucciolo Melo. "CELL THERAPY IN THE TREATMENT OF INTERVERTEBRAL DISC DEGENERATION". Coluna/Columna 20, n.º 2 (junio de 2021): 101–4. http://dx.doi.org/10.1590/s1808-185120212002229178.

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ABSTRACT Approximately 80% of the world population experiences some type of back pain at some point in their life, and in 10% of this population the pain causes chronic disability resulting in a high cost for the treatment of these patients, in addition to compromising their work and social interaction abilities. Current treatment strategies include the surgical procedure for degenerated intervertebral disc resection, the nerve root block and physiotherapy. However, such treatments only relieve symptoms and do not prevent the degeneration of intervertebral discs. Therefore, new therapeutic strategies have emerged and include manipulating cells to recover the degenerated disc. This article will discuss the possible cell therapy alternatives used in the disc regeneration process, featuring a descriptive study of translational medicine that involves clinical aspects of new treatment alternatives and knowledge of basic research areas, such as cellular and molecular biology. Level of evidence V; Expert Opinion.

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