scholarly journals Extracellular Vesicles Derived From Stem Cells in Intervertebral Disc Degeneration

Author(s):  
Xinjie Wu ◽  
Wei Sun

Intervertebral disc degeneration (IVDD) is the leading cause of low back pain related to degradation of cartilaginous tissues, mainly resulting from oxidative stress, cell apoptosis, and extracellular matrix degradation. Extracellular vesicles (EVs) exist in all bodily fluids and can be produced by all types of cells. Stem cell-derived EVs (SC-EVs), which are the main paracrine components of stem cells, have gained significant attention in the field of regenerative medicine. Over the past years, accumulating evidence indicates the therapeutic and diagnostic potentials of EVs in IVDD. The main mechanisms involve the induction of regenerative phenotypes, apoptosis alleviation, and immune modulation. In addition, the efficiency of SC-EVs can be enhanced by choosing appropriate donor cells and cell phenotypes, optimizing cell culture conditions, or engineering EVs to deliver drugs and targeting molecules. Given the importance and novelty of SC-EVs, we give an overview of SC-EVs and discuss the roles of SC-EVs in IVDD.

2018 ◽  
Vol 10 (1) ◽  
pp. 1 ◽  
Author(s):  
Anna Meiliana ◽  
Nurrani Mustika Dewi ◽  
Andi Wijaya

BACKGROUND: Low back pain (LBP) mostly caused by disc degeneration, reflects to a tremendous of health care system and economy. More knowledge about these underlying pathologies will improve the opportunities that may represent critical therapeutic targets.CONTENT: Basic research is advancing the understanding of the pathogenesis and management of LBP at the molecular and genetic levels. Cytokines such as matrix metalloproteinases, phospholipase A2, nitric oxide, and tumor necrosis factor-α are thought to contribute to the development of LBP. Mesenchymal stem cells (MSCs) transplant to cartilage-like cells and secrete extracellular matrix and encourage nucleus pulposus (NP) cell activity inhibiting NP cell apoptosis, together with some chemical mediators such as cytokines and growth factors become a safe and effective new strategy for intervertebral disc degeneration (IDD) treatment and regeneration.SUMMARY: IDD occurs where there is a loss of homeostatic balance with a predominantly catabolic metabolic profile. A basic understanding of the molecular changes occurring in the degenerating disc is important for practicing clinicians to help them to inform patients to alter lifestyle choices, identify beneficial or harmful supplements, or offer new biologic, genetic, or stem cell therapies.KEYWORDS: low back pain (LBP), intervertebral disc (IVD), degeneration, nucleus pulposus (NP), annulus fibrosus (AF), extracellular matrix (ECM), genetic, stem cells


2021 ◽  
Vol 12 ◽  
pp. 204173142110216
Author(s):  
Shaoqian Cui ◽  
Lei Zhang

Mesenchymal stem cell (MSC)-derived extracellular vesicles (EVs) have been reported to deliver exogenous microRNAs (miRNAs or miRs) to reduce the progression of intervertebral disc degeneration (IDD). The purpose of the current study was to investigate the therapeutic potential of MSC-derived EVs delivering miR-129-5p in IDD. First, miR-129-5p expression levels were quantified in nucleus pulposus (NP) tissues of IDD patients. An IL-1β-induced NP cell model with IDD was then established, and co-cultured with EVs derived from MSCs that had been transfected with miR-129-5p mimic or inhibitor to elucidate the effects of miR-129-5p on cell viability, apoptosis, and ECM degradation. In addition, RAW264.7 cells were treated with the conditioned medium (CM) of NP cells. Next, the expression patterns of polarization markers and those of inflammatory factors in macrophages were detected using flow cytometry and ELISA, respectively. Lastly, rat models of IDD were established to validate the in vitro findings. It was found that miR-129-5p was poorly-expressed in NP tissues following IDD. Delivery of miR-129-5p to NP cells by MSC-derived EVs brought about a decrease in NP cell apoptosis, ECM degradation and M1 polarization of macrophages. Moreover, miR-129-5p directly-targeted LRG1, which subsequently promoted the activation of p38 MAPK signaling pathway, thus polarizing macrophages toward the M1 phenotype. Furthermore, MSC-derived EVs transferring miR-129-5p relieved IDD via inhibition of the LRG1/p38 MAPK signaling in vivo. Altogether, our findings indicated that MSC-derived EVs carrying miR-129-5p confer protection against IDD by targeting LRG1 and suppressing the p38 MAPK signaling pathway, offering a novel theranostic marker in IDD.


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