The Experts below are selected from a list of 56919 Experts worldwide ranked by ideXlab platform
Daisuke Sakai - One of the best experts on this subject based on the ideXlab platform.
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Future perspectives of cell-based therapy for Intervertebral Disc disease
European Spine Journal, 2008Co-Authors: Daisuke SakaiAbstract:Intervertebral Disc degeneration is a primary cause of low back pain and has a high societal cost. Research on cell-based therapies for Intervertebral Disc disease is emerging, along with the interest in biological therapy to treat Disc disease without reducing the mobility of the spinal motion segment. Results from animal models have shown promising results under limited conditions; however, future studies are needed to optimise efficacy, methodology, and safety. To advance research on cell-based therapy for Intervertebral Disc disease, a better understanding of the phenotype and differentiation of Disc cells and of their microenvironment is essential. This article reviews current concepts in cell-based therapy for Intervertebral Disc disease, with updates on potential cell sources tested primarily using animal models, and Discusses the hurdles to clinical application. Future perspectives for cell-based therapies for Intervertebral Disc disease are also Discussed.
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Stem cell applications in Intervertebral Disc repair.
Cellular and molecular biology (Noisy-le-Grand France), 2008Co-Authors: Akihiko Hiyama, Joji Mochida, Daisuke SakaiAbstract:There is increasing rise of interest in stem cell therapy, as it provides new options for treating a broad range of diseases. Several experimental methods are being explored for the use of stem cells in delaying or reversing the degenerative process of the Intervertebral Disc, a major cause of low back pain. In this article, we review the current strategies for stem cell applications in Intervertebral Disc repair and present three novel approaches. These are, first, the activation of nucleus pulposus cells by co-culture with mesenchymal stem cells for autologous Disc cell reinsertion; second, the in vitro induction of nucleus pulposus-like or annulus fibrosus-like cells from mesenchymal stem cells; and third, the in vivo induction study by direct transplantation of mesenchymal stem cells to the Intervertebral Disc induced to degenerate experimentally. Although still untested, stem cell therapy may become a major option in the treatment of Intervertebral Disc degeneration.
Matthew R. Steensma - One of the best experts on this subject based on the ideXlab platform.
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Genetic and Functional Studies of the Intervertebral Disc: A Novel Murine Intervertebral Disc Model
PloS one, 2014Co-Authors: Dominic W. Pelle, Jacqueline D. Peacock, Courtney L. Schmidt, Kevin Kampfschulte, Donald J. Scholten, Scott S. Russo, Kenneth J. Easton, Matthew R. SteensmaAbstract:Intervertebral Disc (IVD) homeostasis is mediated through a combination of micro-environmental and biomechanical factors, all of which are subject to genetic influences. The aim of this study is to develop and characterize a genetically tractable, ex vivo organ culture model that can be used to further elucidate mechanisms of Intervertebral Disc disease. Specifically, we demonstrate that IVD Disc explants (1) maintain their native phenotype in prolonged culture, (2) are responsive to exogenous stimuli, and (3) that relevant homeostatic regulatory mechanisms can be modulated through ex-vivo genetic recombination. We present a novel technique for isolation of murine IVD explants with demonstration of explant viability (CMFDA/propidium iodide staining), Disc anatomy (HE AdCre) following 14 days of culture in DMEM media containing 10% fetal bovine serum, 1% L-glutamine, and 1% penicillin/streptomycin. IVD explants maintained their micro-anatomic integrity, ECM proteoglycan content, viability, and gene expression profile consistent with a homeostatic drive in culture. Treatment of genetically engineered explants with cre-expressing adenovirus efficaciously induced ex vivo genetic recombination in a variety of genetically engineered mouse models. Exogenous administration of IL-1s and TGF-s3 resulted in predicted catabolic and anabolic responses, respectively. Genetic recombination of TGFBR1fl/fl explants resulted in constitutively active TGF-s signaling that matched that of exogenously administered TGF-s3. Our results illustrate the utility of the murine Intervertebral Disc explant to investigate mechanisms of Intervertebral Disc degeneration.
Yasuaki Tokuhashi - One of the best experts on this subject based on the ideXlab platform.
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Transplantation of dedifferentiation fat cells promotes Intervertebral Disc regeneration in a rat Intervertebral Disc degeneration model.
Biochemical and biophysical research communications, 2017Co-Authors: Enshi Nakayama, Taro Matsumoto, Tomohiko Kazama, Koichiro Kano, Yasuaki TokuhashiAbstract:Abstract Our group has reported that mature adipocyte-derived dedifferentiated fat (DFAT) cells show multilineage differentiation potential similar to that observed in mesenchymal stem cells. In the present study, we examined whether DFAT cell transplantation could contribute to Intervertebral Disc regeneration using a rat Intervertebral Disc degeneration (IDD) model. The IDD was created in Sprague-Dawley rats by puncturing at level of caudal Intervertebral Disc under fluoroscopy. One week after injury, rat DFAT cells (5 × 104, DFAT group, n = 13) or phosphate-buffered saline (PBS, control group, n = 13) were injected into the Intervertebral Disc. Percent Disc height index (%DHI) was measured every week and histology of injured Disc was evaluated at 8 weeks after transplantation. Radiographic analysis revealed that the %DHI in the DFAT group significantly higher than that in the control group at 2–3 weeks after transplantation. Histological analysis revealed that ectopic formation of nucleus pulposus (NP)-like tissue at the outer layer of annulus fibrosus was frequently observed in the DFAT group but not in the control group. Transplantation experiments using green fluorescent protein (GFP)-labeled DFAT cells revealed that the ectopic NP-like tissue was positive for GFP, suggesting direct differentiation of DFAT cells into NP-like cells. In conclusion, DFAT cell transplantation promoted the regeneration of Intervertebral Disc and improved Intervertebral Disc height in the rat IDD model. Because adipose tissue is abundant and easily accessible, DFAT cell transplantation may be an attractive therapeutic strategy against IDD.
Dominic W. Pelle - One of the best experts on this subject based on the ideXlab platform.
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Genetic and Functional Studies of the Intervertebral Disc: A Novel Murine Intervertebral Disc Model
PloS one, 2014Co-Authors: Dominic W. Pelle, Jacqueline D. Peacock, Courtney L. Schmidt, Kevin Kampfschulte, Donald J. Scholten, Scott S. Russo, Kenneth J. Easton, Matthew R. SteensmaAbstract:Intervertebral Disc (IVD) homeostasis is mediated through a combination of micro-environmental and biomechanical factors, all of which are subject to genetic influences. The aim of this study is to develop and characterize a genetically tractable, ex vivo organ culture model that can be used to further elucidate mechanisms of Intervertebral Disc disease. Specifically, we demonstrate that IVD Disc explants (1) maintain their native phenotype in prolonged culture, (2) are responsive to exogenous stimuli, and (3) that relevant homeostatic regulatory mechanisms can be modulated through ex-vivo genetic recombination. We present a novel technique for isolation of murine IVD explants with demonstration of explant viability (CMFDA/propidium iodide staining), Disc anatomy (HE AdCre) following 14 days of culture in DMEM media containing 10% fetal bovine serum, 1% L-glutamine, and 1% penicillin/streptomycin. IVD explants maintained their micro-anatomic integrity, ECM proteoglycan content, viability, and gene expression profile consistent with a homeostatic drive in culture. Treatment of genetically engineered explants with cre-expressing adenovirus efficaciously induced ex vivo genetic recombination in a variety of genetically engineered mouse models. Exogenous administration of IL-1s and TGF-s3 resulted in predicted catabolic and anabolic responses, respectively. Genetic recombination of TGFBR1fl/fl explants resulted in constitutively active TGF-s signaling that matched that of exogenously administered TGF-s3. Our results illustrate the utility of the murine Intervertebral Disc explant to investigate mechanisms of Intervertebral Disc degeneration.
James D. Kang - One of the best experts on this subject based on the ideXlab platform.
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Molecular Mechanisms of Intervertebral Disc Degeneration.
Spine surgery and related research, 2018Co-Authors: Sean M Rider, Shuichi Mizuno, James D. KangAbstract:Intervertebral Disc degeneration is a well-known cause of disability, the result of which includes neck and back pain with associated mobility limitations. The purpose of this article is to provide an overview of the known molecular mechanisms through which Intervertebral Disc degeneration occurs as a result of complex interactions of exogenous and endogenous stressors. This review will focus on some of the identified molecular changes leading to the deterioration of the extracellular matrix of both the annulus fibrosus and nucleus pulposus. In addition, we will provide a summation of our current knowledge supporting the role of associated DNA and intracellular damage, cellular senescence's catabolic effects, oxidative stress, and the cell's inappropriate response to damage in contributing to Intervertebral Disc degeneration. Our current understanding of the molecular mechanisms through which Intervertebral Disc degeneration occurs provides us with abundant insight into how physical and chemical changes exacerbate the degenerative process of the entire spine. Furthermore, we will describe some of the related molecular targets and therapies that may contribute to Intervertebral repair and regeneration.
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Advances in gene therapy for Intervertebral Disc degeneration
The Spine Journal, 2004Co-Authors: Robert C. Chadderdon, Adam L. Shimer, Lars G. Gilbertson, James D. KangAbstract:Abstract Background context Gene therapy is a growing concept in many fields of medicine, and its potential applications are numerous. With a growing understanding of the molecular and cellular biology of Intervertebral Disc degeneration, alternatives to current treatment options are under investigation. Gene therapy offers an exciting new direction in the treatment of Intervertebral Disc degeneration, and potential targets of genetic alteration are being explored. Purpose To describe and update the recent advances in research on gene therapy for the treatment of Intervertebral Disc degeneration. Study design/setting Review of current research for the application of gene therapy as potential treatment for Intervertebral Disc degeneration. Methods Literature review. Results There is a growing body of research pertaining to the use of gene therapy as an adjunct or alternative to the current treatment options for Intervertebral Disc degeneration. In vitro studies have demonstrated that transfer of cDNA encoding growth factors to Intervertebral Disc cells can favorably modify their metabolic and biological functions. Additionally, initial in vivo studies have demonstrated successful transduction of growth factors to the Intervertebral Disc with confirmed upregulation of extracellular matrix synthesis. Investigators continue to explore the potential of gene therapy with several factors for the treatment of Intervertebral Disc degeneration. Conclusions The potential of gene therapy to alter the course of Intervertebral Disc degeneration holds much clinical promise and continues to stimulate further investigations.
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Advances in gene therapy for Intervertebral Disc degeneration.
The spine journal : official journal of the North American Spine Society, 2004Co-Authors: Robert C. Chadderdon, Adam L. Shimer, Lars G. Gilbertson, James D. KangAbstract:Gene therapy is a growing concept in many fields of medicine, and its potential applications are numerous. With a growing understanding of the molecular and cellular biology of Intervertebral Disc degeneration, alternatives to current treatment options are under investigation. Gene therapy offers an exciting new direction in the treatment of Intervertebral Disc degeneration, and potential targets of genetic alteration are being explored. To describe and update the recent advances in research on gene therapy for the treatment of Intervertebral Disc degeneration. Review of current research for the application of gene therapy as potential treatment for Intervertebral Disc degeneration. Literature review. There is a growing body of research pertaining to the use of gene therapy as an adjunct or alternative to the current treatment options for Intervertebral Disc degeneration. In vitro studies have demonstrated that transfer of cDNA encoding growth factors to Intervertebral Disc cells can favorably modify their metabolic and biological functions. Additionally, initial in vivo studies have demonstrated successful transduction of growth factors to the Intervertebral Disc with confirmed upregulation of extracellular matrix synthesis. Investigators continue to explore the potential of gene therapy with several factors for the treatment of Intervertebral Disc degeneration. The potential of gene therapy to alter the course of Intervertebral Disc degeneration holds much clinical promise and continues to stimulate further investigations.
