scholarly journals Exosomes from mesenchymal stem cells modulate endoplasmic reticulum stress to protect against nucleus pulposus cell death and ameliorate intervertebral disc degeneration in vivo

Theranostics ◽  
2019 ◽  
Vol 9 (14) ◽  
pp. 4084-4100 ◽  
Author(s):  
Zhiwei Liao ◽  
Rongjin Luo ◽  
Gaocai Li ◽  
Yu Song ◽  
Shengfeng Zhan ◽  
...  
Keyword(s):  
Stem Cells ◽  
Endoplasmic Reticulum ◽  
Cell Death ◽  
Mesenchymal Stem Cells ◽  
Endoplasmic Reticulum Stress ◽  
Intervertebral Disc ◽  
Nucleus Pulposus ◽  
Intervertebral Disc Degeneration ◽  
Nucleus Pulposus Cell

scholarly journals Autophagic Degradation of Gasdermin D Protects against Nucleus Pulposus Cell Pyroptosis and Retards Intervertebral Disc Degeneration In Vivo

2021 ◽  
Vol 2021 ◽  
pp. 1-22
Author(s):  
Zhiwei Liao ◽  
Suyun Li ◽  
Rong Liu ◽  
Xiaobo Feng ◽  
Yunsong Shi ◽  
...  
Keyword(s):  
Cell Death ◽  
Intervertebral Disc ◽  
Nucleus Pulposus ◽  
Disc Degeneration ◽  
Intervertebral Disc Degeneration ◽  
Degradation Mechanism ◽  
Nucleus Pulposus Cell ◽  
Social Burden ◽  
Related Proteins

Intervertebral disc degeneration (IDD) is the primary culprit of low back pain and renders heavy social burden worldwide. Pyroptosis is a newly discovered form of programmed cell death, which is also involved in nucleus pulposus (NP) cells during IDD progression. Moderate autophagy activity is critical for NP cell survival, but its relationship with pyroptosis remains unknown. This study is aimed at investigating the relationship between autophagy and pyroptotic cell death. The pyroptosis executor N-terminal domain of gasdermin D (GSDMD-N) and inflammation-related proteins were measured in lipopolysaccharide- (LPS-) treated human NP cells. Inhibition of autophagy by siRNA transfection and chemical drugs aggravated human NP cell pyroptosis. Importantly, we found that the autophagy-lysosome pathway and not the proteasome pathway mediated the degradation of GSDMD-N as lysosome dysfunction promoted the accumulation of cytoplasmic GSDMD-N. Besides, P62/SQSTM1 colocalized with GSDMD-N and mediated its degradation. The administration of the caspase-1 inhibitor VX-765 could reduce cell pyroptosis as confirmed in a rat disc IDD model in vivo, whereas ATG5 knockdown significantly accelerated the progression of IDD. In conclusion, our study indicated that autophagy protects against LPS-induced human NP cell pyroptosis via a P62/SQSTM1-mediated degradation mechanism and the inhibition of pyroptosis retards IDD progression in vivo. These findings deepen the understanding of IDD pathogenesis and hold implications in unraveling therapeutic targets for IDD treatment.

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 CGRP Regulates Nucleus Pulposus Cell Apoptosis and Inflammation via the MAPK/NF-κB Signaling Pathways during Intervertebral Disc Degeneration

2021 ◽  
Vol 2021 ◽  
pp. 1-19
Author(s):  
Kaiqiang Sun ◽  
Jian Zhu ◽  
Chen Yan ◽  
Fudong Li ◽  
Fanqi Kong ◽  
...  
Keyword(s):  
Intervertebral Disc ◽  
Signaling Pathways ◽  
Nucleus Pulposus ◽  
Disc Degeneration ◽  
Intervertebral Disc Degeneration ◽  
Nucleus Pulposus Cell ◽  
Mapk Signaling ◽  
Discogenic Pain

Chronic low back pain (CLBP) has been proved to be the dominating cause of disability in patients with lumbar degenerative diseases. Of the various etiological factors, intervertebral disc degeneration (IVDD) has been the dominating cause. In the past few decades, the role and changes of nerve systems, especially the peripheral sensory fibers and their neurotransmitters, in the induction and progression of IVDD have attracted growing concerns. The expression of many neuropeptides, such as SP, NPY, and CGRP, in the nociceptive pathways is increased during the progression of IVDD and responsible for the discogenic pain. Here, the role of CGRP in the progression of IVDD was firstly investigated both in vitro and in vivo. Firstly, we confirmed that human degenerated intervertebral disc tissue exhibited elevated expression of CGRP and its receptor. Secondly, in vitro experiments suggested that CGRP could inhibit the proliferation and induce apoptosis in human nucleus pulposus (NP) cells, as well as promote inflammation and degenerated phenotypes through activating NF-κB and MAPK signaling pathways. Thirdly, CGRP receptor antagonist, Rimegepant, can ameliorate the adverse effects of CGRP imposed on NP cells, which were confirmed in vitro and in vivo. Our results will bring about a brand-new insight into the roles of neuromodulation in IVDD and related therapeutic attempts.

scholarly journals Fe3O4@polydopamine Nanoparticle-Labeled Umbilical Cord Mesenchymal Stem Cells Arrest Intervertebral Disc Degeneration by Enhancing Cell Migration

2021 ◽  
Author(s):  
Meng Zhang ◽  
Butain Zhang ◽  
Ran Li ◽  
Te Liu ◽  
Jun Zhang ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Intervertebral Disc ◽  
Umbilical Cord ◽  
Disc Degeneration ◽  
Intervertebral Disc Degeneration ◽  
Type Ii Collagen ◽  
Systemic Delivery ◽  
Cell Therapies

Abstract Cell therapies for intervertebral disc degeneration (IDD) are intended to replace lost intervertebral disc (IVD) cells. The key to this treatment is to promote the migration of transplanted cells to the lesion site. The purpose of this study was to evaluate the repair effect of umbilical cord mesenchymal stem cells (UCMSCs) labeled with Fe3O4@polydopamine nanoparticles (Fe3O4@PDA NPs) on rat caudal vertebra disc degeneration. We characterized UCMSCs labeled with Fe3O4@PDA NPs, analyzed the effects of nanoparticles on UCMSCs and evaluated UCMSCs labeled with Fe3O4@PDA NPs to repair IDD in vivo. We found that UCMSC Fe3O4@PDA NPs could enhanced the migration of UCMSCs by up-regulating the expression of CXC chemokine receptor type 4 (CXCR4) without effecting UCMSC functionality and the Fe3O4@PDA NPs-labeled UCMSC group had better disc height, better tissue morphology performance and a higher number of transplanted cells and induced notably better regeneration of IVD, evidenced by the higher expression of aggrecan, type II collagen, and Sox-9 and lower expression of Mmp-13, Tnf-α and Il-1β at both mRNA and protein levels than the unlabeled group. We demonstrated systemic delivery of UCMSCs labeled with Fe3O4@PDA NPs could be an appropriate protocol for accelerating and optimizing clinically applicable UCMSC treatment for IDD.

scholarly journals The Differential Effects of Leukocyte-Containing and Pure Platelet-Rich Plasma on Nucleus Pulposus-Derived Mesenchymal Stem Cells: Implications for the Clinical Treatment of Intervertebral Disc Degeneration

2018 ◽  
Vol 2018 ◽  
pp. 1-12 ◽  
Author(s):  
Jun Jia ◽  
Shan-zheng Wang ◽  
Liang-yu Ma ◽  
Jia-bin Yu ◽  
Yu-dong Guo ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Intervertebral Disc ◽  
Nucleus Pulposus ◽  
Disc Degeneration ◽  
Intervertebral Disc Degeneration ◽  
Platelet Rich Plasma ◽  
Enzyme Linked Immunosorbent Assay ◽  
Stem Cell Markers

Background. Platelet-rich plasma (PRP) is a promising strategy for intervertebral disc degeneration. However, the potential harmful effects of leukocytes in PRP on nucleus pulposus-derived mesenchymal stem cells (NPMSCs) have seldom been studied. This study aimed at comparatively evaluating effects of pure platelet-rich plasma (P-PRP) and leukocyte-containing platelet-rich plasma (L-PRP) on rabbit NPMSCs in vitro. Methods. NPMSCs isolated from rabbit NP tissues were treated with L-PRP or P-PRP in vitro, and then cell proliferation and expression of stem cell markers, proinflammatory cytokines (TNF-α, IL-1β), production of ECM (extracellular matrix-related protein), and NF-κB p65 protein were validated by CCK-8 assay, real-time polymerase chain reaction, enzyme-linked immunosorbent assay, immunofluorescence, and western blot respectively. Results. NPMSCs differentiate into nucleus pulposus-like cells after treatment of PRPs (P-PRP and L-PRP), and NPMSCs exhibited maximum proliferation at a 10% PRP dose. L-PRP had observably higher concentration of leukocytes, TNF-α, and IL-1β than P-PRP. Furthermore, compared to P-PRP, L-PRP induced the differentiated NPMSCs to upregulate the expression of TNF-α and IL-1β, enhanced activation of the NF-κB pathway, increased the expression of MMP-1 and MMP-13, and produced less ECM in differentiated NPMSCs. Conclusions. Both P-PRP and L-PRP can induce the proliferation and NP-differentiation of NPMSCs. Compared to L-PRP, P-PRP can avoid the activation of the NF-κB pathway, thus reducing the inflammatory and catabolic responses.

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