Mesenchymal Stem Cell-Derived Extracellular Vesicles: Immunomodulatory Effects and Potential Applications in Intervertebral Disc Degeneration

Hu, Shaojun; Xing, Hongyuan; Zhang, Jiangnan; Zhu, Zemin; Yin, Ying; Zhang, Ning; Qi, Yiying

doi:10.1155/2022/7538025

Cited by 15 publications

(20 citation statements)

References 135 publications

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“…Exosomes deliver drugs to their target sites because of their natural targeting competence, and immense ability to permeate biological barriers. The bioactive substances that are delivered by exosomes are easily degraded via multiple pathways [64]. Therefore, interest in the use of exosomes for disc regeneration is increasing [160].…”

Section: Discussionmentioning

confidence: 99%

“…Since MSCs do not express major histocompatibility complex-II (MHC-II) and costimulatory molecules such as CD 86, CD40, and CD80, they are considered immune-privileged cells [61]. MSCs, which have high regenerative, anti-inflammatory, anti-apoptotic, anti-angiogenic, anti-fibrotic and immunomodulatory abilities, can repair tissue damage and regulate cellular immunity by producing various types of bioactive molecules, such as platelet-derived growth factor (PDGF), matrix metalloproteinase-9 (MMP-9), matrix metalloproteinase-2 (MMP-2), interleukin-6 (IL-6), and insulin-like growth factor-1 (IGF-1) when they come into contact with a suitable host [62][63][64]. In the present scenario, MSCs are considered safe and show drastic therapeutic relevance in the sector of regenerative medicine [65].…”

Section: Mesenchymal Stem Cell Therapy In Ivddmentioning

confidence: 99%

“…Various pro-inflammatory cytokines such as chemokine (C-C motif) ligands 545 (CCL545), chemokine (C-C motif) ligands 4 (CCL4), chemokine (C-C motif) ligands 3 (CCL3), chemokine (C-X-C motif) ligand 1 (CXCL1), and chemokine (C motif) ligand (XCL1) are produced by degenerative disc cells themselves during the process of IVDD, these cytokines attract other leukocytes, resulting in the production of pro-inflammatory cytokines such as TNF-α, IL-1, IL-2, IL-6, and IL-8, which upregulate the matrix catabolic enzymes, causing IVDD to take place quickly [149]. Triggering of these cytokines give rise to a series of pathologic responses in the IVD, causing autophagy, senescence, and apoptosis [64]. Exosomes from MSCs played an anti-inflammatory role in treating pathological NPCs by suppressing inflammatory mediators and NLRP3 inflammasome activation in the rabbit model of IVDD.…”

Section: Anti-inflammatory Activitymentioning

confidence: 99%

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Mesenchymal Stem Cell-Derived Exosomes and Intervertebral Disc Regeneration: Review

Bhujel

Shin

Choi

et al. 2022

IJMS

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Intervertebral disc degeneration (IVDD) is a common cause of lower back pain (LBP), which burdens individuals and society as a whole. IVDD occurs as a result of aging, mechanical trauma, lifestyle factors, and certain genetic abnormalities, leads to loss of nucleus pulposus, alteration in the composition of the extracellular matrix, excessive oxidative stress, and inflammation in the intervertebral disc. Pharmacological and surgical interventions are considered a boon for the treatment of IVDD, but the effectiveness of those strategies is limited. Mesenchymal stem cells (MSCs) have recently emerged as a possible promising regenerative therapy for IVDD due to their paracrine effect, restoration of the degenerated cells, and capacity for differentiation into disc cells. Recent investigations have shown that the pleiotropic effect of MSCs is not related to differentiation capacity but is mediated by the secretion of soluble paracrine factors. Early studies have demonstrated that MSC-derived exosomes have therapeutic potential for treating IVDD by promoting cell proliferation, tissue regeneration, modulation of the inflammatory response, and reduced apoptosis. This paper highlights the current state of MSC-derived exosomes in the field of treatment of IVDD with further possible future developments, applications, and challenges.

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Section: Discussionmentioning

confidence: 99%

Section: Mesenchymal Stem Cell Therapy In Ivddmentioning

confidence: 99%

Section: Anti-inflammatory Activitymentioning

confidence: 99%

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Mesenchymal Stem Cell-Derived Exosomes and Intervertebral Disc Regeneration: Review

Bhujel

Shin

Choi

et al. 2022

IJMS

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“…To be specific, the invagination of the plasma membrane is accompanied by cell-surface proteins and soluble proteins, and early endosomes are formed with the participation of the trans-Golgi network and the endoplasmic reticulum ( Jan et al, 2019 ). Subsequently, early endosomes mature into late endosomes through vector selection ( Hu et al, 2022 ). The endosomal sorting complex required for transport (ESCRT) accounting for the transport mechanism can direct the biogenesis of exosomes, and ESCRT-0 recognizes ubiquitinated goods and initiates the pathway.…”

Section: Exosomes and Exosomal Mirnasmentioning

confidence: 99%

Exosomes and exosomal miRNAs: A new therapy for intervertebral disc degeneration

Wu²,

Tan

et al. 2022

Front. Pharmacol.

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Low back pain has been found as a major cause of global disease burden and disability. Intervertebral disc degeneration is recognized as the vital factor causing low back pain. Intervertebral disc degeneration has a complex mechanism and cannot be avoided. Traditional strategies for the treatment of intervertebral disc degeneration cannot meet the needs of intervertebral disc regeneration, so novel treatment methods are urgently required. Exosomes refer to extracellular vesicles that can be released by most cells, and play major roles in intercellular material transport and information transmission. MicroRNAs have been identified as essential components in exosomes, which can be selectively ingested by exosomes and delivered to receptor cells for the regulation of the physiological activities and functions of receptor cells. Existing studies have progressively focused on the role of exosomes and exosomal microRNAs in the treatment of intervertebral disc degeneration. The focus on this paper is placed on the changes of microenvironment during intervertebral disc degeneration and the biogenesis and mechanism of action of exosomes and exosomal microRNAs. The research results and deficiencies of exosomes and exosomal microRNAs in the regulation of apoptosis, extracellular matrix homeostasis, inflammatory response, oxidative stress, and angiogenesis in intervertebral disc degeneration are primarily investigated. The aim of this paper is to identify the latest research results, potential applications and challenges of this emerging treatment strategy.

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“…Mesenchymal stromal cells have also been explored in this context. 23,24 NCs have previously been shown to be sensitive to substrate stiffness, preferring softer ones. 25,26 Gels designed for cell transplantation and biological regeneration of IVDs may therefore need to be softer than gels intended for purely mechanical restoration purposes.…”

mentioning

confidence: 99%

Semi‐synthetic degradable notochordal cell‐derived matrix hydrogel for use in degenerated intervertebral discs: Initial in vitro characterization

Schmitz

Genabeek

Pouderoijen

et al. 2023

J Biomedical Materials Res

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Low back pain is the leading cause of disability worldwide, but current therapeutic interventions are palliative or surgical in nature. Loss of notochordal cells (NCs) and degradation of the healthy matrix in the nucleus pulposus (NP), the central tissue of intervertebral discs (IVDs), has been associated with onset of degenerative disc changes. Recently, we established a protocol for decellularization of notochordal cell derived matrix (NCM) and found that it can provide regenerative cues to nucleus pulposus cells of the IVD. Here, we combined the biologically regenerative properties of decellularized NCM with the mechanical tunability of a poly(ethylene glycol) hydrogel to additionally address biomechanics in the degenerate IVD. We further introduced a hydrolysable PEG‐diurethane crosslinker for slow degradation of the gels in vivo. The resulting hydrogels were tunable over a broad range of stiffness's (0.2 to 4.5 kPa), matching that of NC‐rich and ‐poor NP tissues, respectively. Gels formed within 30 min, giving ample time for handling, and remained shear‐thinning post‐polymerization. Gels also slowly released dNCM over 28 days as measured by GAG effusion. Viability of encapsulated bone marrow stromal cells after extrusion through a needle remained high. Although encapsulated NCs stayed viable over two weeks, their metabolic activity decreased, and their phenotype was lost in physiological medium conditions in vitro. Overall, the obtained gels hold promise for application in degenerated IVDs but require further tuning for combined use with NCs.

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Mesenchymal Stem Cell-Derived Extracellular Vesicles: Immunomodulatory Effects and Potential Applications in Intervertebral Disc Degeneration

Cited by 15 publications

References 135 publications

Mesenchymal Stem Cell-Derived Exosomes and Intervertebral Disc Regeneration: Review

Mesenchymal Stem Cell-Derived Exosomes and Intervertebral Disc Regeneration: Review

Exosomes and exosomal miRNAs: A new therapy for intervertebral disc degeneration

Semi‐synthetic degradable notochordal cell‐derived matrix hydrogel for use in degenerated intervertebral discs: Initial in vitro characterization

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