Response of Mesenchymal Stem Cells and Intervertebral Disc Cells to Inflammatory Challenge

2011 ◽  
Author(s):  
Neena Rajan ◽  
Nathaniel Stetson ◽  
Passquale Razzano ◽  
Mitchell Levine ◽  
Daniel Grande ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Intervertebral Disc ◽  
Disc Disease ◽  
Clinical Model ◽  
Injury Model ◽  
Tnf Α ◽  
Disc Cells ◽  
Ivd Degeneration ◽  
Pro Inflammatory Cytokines

Human intervertebral disc (IVD) degeneration is accompanied by elevated levels of pro-inflammatory cytokines, particularly IL-1β and TNF-α [1–3]. Cytokine secretion by disc cells increases catabolic breakdown of the tissue, resulting in a positive feedback of disc integrity loss and further inflammation [4–6]. A recent study by our group has shown that severity of degeneration in an injury model can influence the therapeutic effect of cell based repair, such as treatment with mesenchymal stem cells (MSCs) [7]. The goal of this study is to measure the response of MSCs to inflammatory challenge, and to compare this response to that of differentiated disc cells from the nucleus pulposus (NP), annulus fibrosis (AF) and end plate (EP). In this study, we investigated the effects of lipopolysaccharide (LPS) on intervertebral disc cells and MSCs viability, pro-inflammatory cytokine expression and extracellular matrix (ECM) expression. LPS is an endotoxin that induces strong immune responses in animal tissue and hence widely used as a pre-clinical model of inflammation. This approach provides an opportunity to study broad aspects of the physiological inflammatory process observed in degenerative disc disease.

scholarly journals Injectable Hydrogel Combined with Nucleus Pulposus-Derived Mesenchymal Stem Cells for the Treatment of Degenerative Intervertebral Disc in Rats

2019 ◽  
Vol 2019 ◽  
pp. 1-17 ◽  
Author(s):  
Feng Wang ◽  
Li-ping Nan ◽  
Shi-feng Zhou ◽  
Yang Liu ◽  
Ze-yu Wang ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Intervertebral Disc ◽  
Nucleus Pulposus ◽  
Rat Model ◽  
Injectable Hydrogel ◽  
Cell Scaffold ◽  
Ivd Degeneration

Stem cell-based tissue engineering in treating intervertebral disc (IVD) degeneration is promising. An appropriate cell scaffold can maintain the viability and function of transplanted cells. Injectable hydrogel has the potential to be an appropriate cell scaffold as it can mimic the condition of the natural extracellular matrix (ECM) of nucleus pulposus (NP) and provide binding sites for cells. This study was aimed at investigating the effect of injectable hydrogel-loaded NP-derived mesenchymal stem cells (NPMSC) for the treatment of IVD degeneration (IDD) in rats. In this study, we selected injectable 3D-RGD peptide-modified polysaccharide hydrogel as a cell transplantation scaffold. In vitro, the biocompatibility, microstructure, and induced differentiation effect on NPMSC of the hydrogel were studied. In vivo, the regenerative effect of hydrogel-loaded NPMSC on degenerated NP in a rat model was evaluated. The results showed that NPMSC was biocompatible and able to induce differentiation in hydrogel in vivo. The disc height index (almost 87%) and MRI index (3313.83±227.79) of the hydrogel-loaded NPMSC group were significantly higher than those of other groups at 8 weeks after injection. Histological staining and immunofluorescence showed that the hydrogel-loaded NPMSC also partly restored the structure and ECM content of degenerated NP after 8 weeks. Moreover, the hydrogel could support long-term NPMSC survival and decrease cell apoptosis rate of the rat IVD. In conclusion, injectable hydrogel-loaded NPMSC transplantation can delay the level of IDD and promote the regeneration of the degenerative IVD in the rat model.

scholarly journals For whom the disc tolls: intervertebral disc degeneration, back pain and toll-like receptors

2021 ◽  
Vol 41 ◽  
pp. 355-369
Author(s):  
DG Bisson ◽  
◽  
M Mannarino ◽  
R Racine ◽  
L Haglund
Keyword(s):  
Back Pain ◽  
Intervertebral Disc ◽  
Inflammatory Cytokines ◽  
Chronic Back Pain ◽  
Proteolytic Enzymes ◽  
Treatment Modalities ◽  
Toll Like Receptors ◽  
Disc Cells ◽  
Ivd Degeneration ◽  
Pro Inflammatory Cytokines

Intervertebral disc (IVD) degeneration is characterised by catabolic and inflammatory processes that contribute largely to tissue degradation and chronic back pain. The disc cells are responsible for the pathological production of pro-inflammatory cytokines and catabolic enzymes leading to degeneration. However, this phenotypical change is poorly understood. Growing evidence in animal and human studies implicates Toll-like receptors (TLR) and their activation through danger-associated alarmins, found increasingly in degenerating IVDs. TLR signalling results in the release of pro-inflammatory cytokines and proteolytic enzymes that can directly cause IVD degeneration and back pain. This review aims to summarise the current literature on TLR activation in IVD degeneration and discuss potential treatment modalities to alleviate the inflammatory phenotype of disc cells in order to arrest IVD degeneration and back pain.

Regeneration Potential of Stem Cell in the Treatment of IVD

2021 ◽  
Vol 9 (8) ◽  
pp. 3022-3036
Author(s):  
Riya Bhanushali
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Stem Cell ◽  
Cell Therapy ◽  
Intervertebral Disc ◽  
Stem Cell Therapy ◽  
Degenerative Disc Disease ◽  
Disc Disease ◽  
Degenerative Disc ◽  
Potential Use

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

scholarly journals Pioglitazone Protects Compression-Mediated Apoptosis in Nucleus Pulposus Mesenchymal Stem Cells by Suppressing Oxidative Stress

2019 ◽  
Vol 2019 ◽  
pp. 1-14 ◽  
Author(s):  
Yiqiang Hu ◽  
Liang Huang ◽  
Min Shen ◽  
Yunlu Liu ◽  
Guohui Liu ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Intervertebral Disc ◽  
Nucleus Pulposus ◽  
Cellular Therapy ◽  
Adverse Outcomes ◽  
Protective Effects ◽  
Apoptosis Pathway ◽  
Ivd Degeneration

Excessive compression, the main cause of intervertebral disc (IVD) degeneration, affected endogenous repair of the intervertebral disc. Pioglitazone (PGZ) is the agonist of peroxisome proliferator-activated receptor γ, which has been widely used in the treatment of diabetes mellitus. The present study aim at investigating whether pioglitazone has protective effects on compression-mediated cell apoptosis in nucleus pulposus mesenchymal stem cells (NP-MSCs) and further exploring the possible underlying mechanism. Our results indicated that the isolated cells satisfied the criteria of MSC stated by the International Society for Cellular Therapy. Besides, our research revealed that pioglitazone could protect cell viability, cell proliferation of NP-MSCs and alleviated the toxic effects caused by compression. The actin stress fibers was suppressed obviously under compression, and pioglitazone alleviated the adverse outcomes. Pioglitazone exerted protective effects on compression-induced NP-MSCs apoptosis according to annexin V/PI double-staining and TUNEL assays. Pioglitazone suppressed compression-induced NP-MSCs oxidative stress, including decreasing compression-induced overproduction of reactive oxygen species (ROS) and malondialdehyde (MDA), and alleviated compression-induced mitochondrial membrane potential (MMP) decrease. Ultrastructure collapse of the mitochondria exhibited a notable improvement by pioglitazone in compression-induced NP-MSCs according to transmission electron microscopy (TEM). Furthermore, the molecular results showed that pioglitazone significantly decreased the expression of apoptosis-associated proteins, including cyto.cytochrome c, Bax, cleaved caspase-9, and cleaved caspase-3, and promoted Bcl-2 expression. These results indicated that pioglitazone alleviated compression-induced NP-MSCs apoptosis by suppressing oxidative stress and the mitochondrial apoptosis pathway, which may be a valuable candidate for the treatment of IVD degeneration.

scholarly journals Inflammatory cytokines-stimulated human muscle stem cells ameliorate ulcerative colitis via the IDO-TSG6 axis

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Shengchao Zhang ◽  
Jiankai Fang ◽  
Zhanhong Liu ◽  
Pengbo Hou ◽  
Lijuan Cao ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Inflammatory Cytokines ◽  
Human Muscle ◽  
Enzyme Linked Immunosorbent Assay ◽  
Muscle Stem Cells ◽  
Tnf Α ◽  
Ifn Γ ◽  
Anti Inflammatory

Abstract Background Muscle stem cells (MuSCs) are absolutely required for the formation, repair, and regeneration of skeletal muscle tissue. Increasing evidence demonstrated that tissue stem cells, especially mesenchymal stem cells (MSCs), can exert therapeutic effects on various degenerative and inflammatory disorders based on their immunoregulatory properties. Human mesenchymal stem cells (hMSCs) treated with interferon-γ (IFN-γ) and tumor necrosis factor-α (TNF-α) were reported to possess anti-inflammatory functions by producing TNF-stimulated gene 6 (TSG-6). However, whether human muscle stem cells (hMuSCs) also possess TSG-6 mediated anti-inflammatory functions has not been explored. Methods The ulcerative colitis mouse model was established by subjecting mice to dextran sulfate sodium (DSS) in drinking water for 7 days. hMuSCs were pretreated with IFN-γ and TNF-α for 48 h and were then transplanted intravenously at day 2 of DSS administration. Body weights were monitored daily. Indoleamine 2,3-dioxygenase (IDO) and TSG-6 in hMuSCs were knocked down with short hairpin RNA (shRNA) and small interfering RNA (siRNA), respectively. Colon tissues were collected for length measurement and histopathological examination. The serum level of IL-6 in mice was measured by enzyme-linked immunosorbent assay (ELISA). Real-time PCR and Western blot analysis were performed to evaluate gene expression. Results hMuSCs treated with inflammatory factors significantly ameliorated inflammatory bowel disease (IBD) symptoms. IDO and TSG-6 were greatly upregulated and required for the beneficial effects of hMuSCs on IBD. Mechanistically, the tryptophan metabolites, kynurenine (KYN) or kynurenic acid (KYNA) produced by IDO, augmented the expression of TSG-6 through activating their common receptor aryl hydrocarbon receptor (AHR). Conclusion Inflammatory cytokines-treated hMuSCs can alleviate DSS-induced colitis through IDO-mediated TSG-6 production.

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