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Intervertebral Disc Degeneration and Its Regeneration

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A special issue of Cells (ISSN 2073-4409).

Deadline for manuscript submissions: closed (10 September 2023) | Viewed by 12910

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Special Issue Editor

Dr. Hideki Sudo

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Guest Editor

Department of Advanced Medicine for Spine and Spinal Cord Disorders, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Sapporo, Hokkaido 060-0808, Japan
Interests: spine; intervertebral disc; biomaterial; stem cell; gene therapy; information technology
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Special Issue Information

Dear Colleagues,

The increasing incidence of intervertebral disc (IVD) degeneration with age and its correlation with lower back pain, IVD herniation, and spinal canal stenosis is a remarkable trend in contemporary society. Although surgical treatments, such as discectomy and spinal fusion, are effective strategies, several complications have been reported, including reherniation and adjacent segment disease. These treatments do not focus on the etiology of IVD degeneration, which is poorly understood. Therefore, a novel and fundamental approach to treating IVD degeneration is highly anticipated.

Dysfunction is caused by degeneration in the IVDs as a result of several factors, including injury, aging, apoptosis of the nucleus pulposus, and mechanical overload, leading to diminished organization and repair of the extracellular matrix.

Biological methods of IVD repair have gained interest as alternative options to restoring degenerated IVDs using growth factor proteins to stimulate cell activity and increase extracellular matrix synthesis. Alternatively, to overcome the rapid biological clearance, some studies have demonstrated gene transfer into nucleus pulposus cells, which provides a continuous synthesis of therapeutic proteins. In addition, the injection of hydrogels or stem cells has been attempted in basic and translational research.

This Special Issue aims to summarize the current knowledge on the degeneration and regeneration of IVD.

We look forward to your contributions.

Prof. Dr. Hideki Sudo
Guest Editor

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Keywords

intervertebral disc degeneration
regeneration
biomaterial
stem cell
gene therapy

Published Papers (3 papers)

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Research

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24 pages, 7961 KiB

Open AccessArticle

Protective Effects of Growth Differentiation Factor-6 on the Intervertebral Disc: An In Vitro and In Vivo Study

by Kunihiko Miyazaki, Shingo Miyazaki, Takashi Yurube, Yoshiki Takeoka, Yutaro Kanda, Zhongying Zhang, Yuji Kakiuchi, Ryu Tsujimoto, Hiroki Ohnishi, Tomoya Matsuo, Masao Ryu, Ryosuke Kuroda and Kenichiro Kakutani

Cells 2022, 11(7), 1174; https://doi.org/10.3390/cells11071174 - 31 Mar 2022

Cited by 6 | Viewed by 2287

Abstract

Growth differentiation factors (GDFs) regulate homeostasis by amplifying extracellular matrix anabolism and inhibiting pro-inflammatory cytokine production in the intervertebral disc (IVD). The aim of this study was to elucidate the effects of GDF-6 on human IVD nucleus pulposus (NP) cells using a three-dimensional culturing system in vitro and on rat tail IVD tissues using a puncture model in vivo. In vitro, Western blotting showed decreased GDF-6 expression with age and degeneration severity in surgically collected human IVD tissues (n = 12). Then, in moderately degenerated human IVD NP cells treated with GDF-6 (100 ng/mL), immunofluorescence demonstrated an increased expression of matrix components including aggrecan and type II collagen. Quantitative polymerase chain reaction analysis also presented GDF-6-induced downregulation of pro-inflammatory tumor necrosis factor (TNF)-α (p = 0.014) and interleukin (IL)-6 (p = 0.016) gene expression stimulated by IL-1β (10 ng/mL). Furthermore, in the mitogen-activated protein kinase pathway, Western blotting displayed GDF-6-induced suppression of p38 phosphorylation (p = 0.041) under IL-1β stimulation. In vivo, intradiscal co-administration of GDF-6 and atelocollagen was effective in alleviating rat tail IVD annular puncture-induced radiologic height loss (p = 0.005), histomorphological degeneration (p < 0.001), matrix metabolism (aggrecan, p < 0.001; type II collagen, p = 0.001), and pro-inflammatory cytokine production (TNF-α, p < 0.001; IL-6, p < 0.001). Consequently, GDF-6 could be a therapeutic growth factor for degenerative IVD disease. Full article

(This article belongs to the Special Issue Intervertebral Disc Degeneration and Its Regeneration)

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Review

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26 pages, 2407 KiB

Open AccessReview

Biomaterials and Cell-Based Regenerative Therapies for Intervertebral Disc Degeneration with a Focus on Biological and Biomechanical Functional Repair: Targeting Treatments for Disc Herniation

by Katsuhisa Yamada, Norimasa Iwasaki and Hideki Sudo

Cells 2022, 11(4), 602; https://doi.org/10.3390/cells11040602 - 9 Feb 2022

Cited by 23 | Viewed by 4371

Abstract

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. Full article

(This article belongs to the Special Issue Intervertebral Disc Degeneration and Its Regeneration)

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17 pages, 1985 KiB

Open AccessFeature PaperReview

Causes of and Molecular Targets for the Treatment of Intervertebral Disc Degeneration: A Review

by Takashi Ohnishi, Norimasa Iwasaki and Hideki Sudo

Cells 2022, 11(3), 394; https://doi.org/10.3390/cells11030394 - 24 Jan 2022

Cited by 44 | Viewed by 5425

Abstract

Intervertebral disc degeneration (IVDD) is a pathological condition that can lead to intractable back pain or secondary neurological deficits. There is no fundamental cure for this condition, and current treatments focus on alleviating symptoms indirectly. Numerous studies have been performed to date, and the major strategy for all treatments of IVDD is to prevent cell loss due to programmed or regulated cell death. Accumulating evidence suggests that several types of cell death other than apoptosis, including necroptosis, pyroptosis, and ferroptosis, are also involved in IVDD. In this study, we discuss the molecular pathway of each type of cell death and review the literature that has identified their role in IVDD. We also summarize the recent advances in targeted therapy at the RNA level, including RNA modulations through RNA interference and regulation of non-coding RNAs, for preventing cell death and subsequent IVDD. Therefore, we review the causes and possible therapeutic targets for RNA intervention and discuss the future direction of this research field. Full article

(This article belongs to the Special Issue Intervertebral Disc Degeneration and Its Regeneration)

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