scholarly journals Genetic Therapy for Intervertebral Disc Degeneration

2021 ◽  
Vol 22 (4) ◽  
pp. 1579 ◽  
Author(s):  
Eun Roh ◽  
Anjani Darai ◽  
Jae Kyung ◽  
Hyemin Choi ◽  
Su Kwon ◽  
...  
Keyword(s):  
Gene Therapy ◽  
Animal Models ◽  
Intervertebral Disc ◽  
Treatment Options ◽  
Mammalian Target Of Rapamycin ◽  
Chronic Lower Back Pain ◽  
Technological Advances ◽  
Disc Cells ◽  
Ivd Degeneration

Intervertebral disc (IVD) degeneration can cause chronic lower back pain (LBP), leading to disability. Despite significant advances in the treatment of discogenic LBP, the limitations of current treatments have sparked interest in biological approaches, including growth factor and stem cell injection, as new treatment options for patients with chronic LBP due to IVD degeneration (IVDD). Gene therapy represents exciting new possibilities for IVDD treatment, but treatment is still in its infancy. Literature searches were conducted using PubMed and Google Scholar to provide an overview of the principles and current state of gene therapy for IVDD. Gene transfer to degenerated disc cells in vitro and in animal models is reviewed. In addition, this review describes the use of gene silencing by RNA interference (RNAi) and gene editing by the clustered regularly interspaced short palindromic repeats (CRISPR) system, as well as the mammalian target of rapamycin (mTOR) signaling in vitro and in animal models. Significant technological advances in recent years have opened the door to a new generation of intradiscal gene therapy for the treatment of chronic discogenic LBP.

Effect of TGF-β3 on the Gene Expression of Intervertebral Disc Cells in 3D Pellet Cultures

2010 ◽  
Author(s):  
C. Houseman ◽  
M. Scro ◽  
S. Belverud ◽  
D. Chen ◽  
P. Razzano ◽  
...  
Keyword(s):  
Intervertebral Disc ◽  
Tissue Regeneration ◽  
Annulus Fibrosus ◽  
Culture System ◽  
Tissue Repair ◽  
Tissue Type ◽  
Disc Cells ◽  
Ivd Degeneration

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).

scholarly journals ROS: Crucial Intermediators in the Pathogenesis of Intervertebral Disc Degeneration

2017 ◽  
Vol 2017 ◽  
pp. 1-12 ◽  
Author(s):  
Chencheng Feng ◽  
Minghui Yang ◽  
Minghong Lan ◽  
Chang Liu ◽  
Yang Zhang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Intervertebral Disc ◽  
Ros Generation ◽  
Antioxidant Supplementation ◽  
The Matrix ◽  
Disc Cells ◽  
Matrix Metabolism ◽  
Ivd Degeneration

Excessive reactive oxygen species (ROS) generation in degenerative intervertebral disc (IVD) indicates the contribution of oxidative stress to IVD degeneration (IDD), giving a novel insight into the pathogenesis of IDD. ROS are crucial intermediators in the signaling network of disc cells. They regulate the matrix metabolism, proinflammatory phenotype, apoptosis, autophagy, and senescence of disc cells. Oxidative stress not only reinforces matrix degradation and inflammation, but also promotes the decrease in the number of viable and functional cells in the microenvironment of IVDs. Moreover, ROS modify matrix proteins in IVDs to cause oxidative damage of disc extracellular matrix, impairing the mechanical function of IVDs. Consequently, the progression of IDD is accelerated. Therefore, a therapeutic strategy targeting oxidative stress would provide a novel perspective for IDD treatment. Various antioxidants have been proposed as effective drugs for IDD treatment. Antioxidant supplementation suppresses ROS production in disc cells to promote the matrix synthesis of disc cells and to prevent disc cells from death and senescence in vitro. However, there is not enough in vivo evidence to support the efficiency of antioxidant supplementation to retard the process of IDD. Further investigations based on in vivo and clinical studies will be required to develop effective antioxidative therapies for IDD.

Are Carbonic Anhydrases Suitable Targets to Fight Protozoan Parasitic Diseases?

2019 ◽  
Vol 25 (39) ◽  
pp. 5266-5278 ◽  
Author(s):  
Katia D'Ambrosio ◽  
Claudiu T. Supuran ◽  
Giuseppina De Simone
Keyword(s):  
Drug Resistance ◽  
Animal Models ◽  
Carbonic Anhydrase ◽  
Drug Target ◽  
Treatment Options ◽  
Parasitic Diseases ◽  
Carbonic Anhydrases ◽  
Extensive Drug Resistance ◽  
Protozoan Infections

Protozoans belonging to Plasmodium, Leishmania and Trypanosoma genera provoke widespread parasitic diseases with few treatment options and many of the clinically used drugs experiencing an extensive drug resistance phenomenon. In the last several years, the metalloenzyme Carbonic Anhydrase (CA, EC 4.2.1.1) was cloned and characterized in the genome of these protozoa, with the aim to search for a new drug target for fighting malaria, leishmaniasis and Chagas disease. P. falciparum encodes for a CA (PfCA) belonging to a novel genetic family, the η-CA class, L. donovani chagasi for a β-CA (LdcCA), whereas T. cruzi genome contains an α-CA (TcCA). These three enzymes were characterized in detail and a number of in vitro potent and selective inhibitors belonging to the sulfonamide, thiol, dithiocarbamate and hydroxamate classes were discovered. Some of these inhibitors were also effective in cell cultures and animal models of protozoan infections, making them of considerable interest for the development of new antiprotozoan drugs with a novel mechanism of action.

Cell shape and gene expression in human intervertebral disc cells: in vitro tissue engineering studies

2003 ◽  
Vol 78 (2) ◽  
pp. 109-117 ◽  
Author(s):  
He Gruber ◽  
Ja Ingram ◽  
K Leslie ◽  
Hj Norton ◽  
En Hanley Jr
Keyword(s):  
Gene Expression ◽  
Tissue Engineering ◽  
Intervertebral Disc ◽  
Cell Shape ◽  
Engineering Studies ◽  
Disc Cells

Glucosamine HCl alters production of inflammatory mediators by rat intervertebral disc cells in vitro

2007 ◽  
Vol 7 (5) ◽  
pp. 601-608 ◽  
Author(s):  
Andrew J.L. Walsh ◽  
Conor W. O'Neill ◽  
Jeffrey C. Lotz
Keyword(s):  
Intervertebral Disc ◽  
Inflammatory Mediators ◽  
Disc Cells

The Effect of Bone Morphogenetic Protein-2 on Rat Intervertebral Disc Cells in Vitro

Spine ◽  
2003 ◽  
Vol 28 (16) ◽  
pp. 1773-1780 ◽  
Author(s):  
S. Tim Yoon ◽  
Keun Su Kim ◽  
Jun Li ◽  
Jin Soo Park ◽  
Tomoyuki Akamaru ◽  
...  
Keyword(s):  
Intervertebral Disc ◽  
Bone Morphogenetic Protein ◽  
Bone Morphogenetic Protein 2 ◽  
Morphogenetic Protein ◽  
Disc Cells

Matrix replenishment by intervertebral disc cells after chemonucleolysis in vitro with chondroitinase ABC and chymopapain

2007 ◽  
Vol 7 (6) ◽  
pp. 694-700 ◽  
Author(s):  
Kazuhiro Chiba ◽  
Koichi Masuda ◽  
Gunnar B.J. Andersson ◽  
Shigeki Momohara ◽  
Eugene J. Thonar
Keyword(s):  
Intervertebral Disc ◽  
Chondroitinase Abc ◽  
Disc Cells
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