Bone mesenchymal stem cell-derived extracellular vesicles promote the repair of intervertebral disc degeneration by transferring microRNA-199a

Wen, Tao; Wang, Hongshen; Li, Yongjin; Lin, Yongpeng; Zhao, Shuai; Liu, Jinggong; Chen, Bolai

doi:10.1080/15384101.2020.1863682

Cited by 39 publications

(37 citation statements)

References 41 publications

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“…Thus, MSC-derived exosomes may reduce the apoptosis in nucleus pulposus cells by antagonizing the signaling pathways involving miRNA-4450 and zinc finger protein 121. Wen et al (2021) also report that miR-199a from MSC exosomes promote the proliferation of NPCs and inhibit cell apoptosis via downregulating GREM1. Moreover, a recent study by our team also testified that exosomes originating from MSC might alleviate apoptosis induced by advanced glycation end products (AGEs) in vitro via activating AKT and ERK signaling pathways ( Liao et al, 2019a ).…”

Section: Impacts Of Msc-derived Exosomes On Ivddmentioning

confidence: 85%

“…Furthermore, subsequent research has proven the strong relationship between miRNAs and the progression of IDD, which partially explains the effective role and its underlying mechanism of MSC exosomes in the IVD ( Zhu G. et al, 2020 ; Wen et al, 2021 ). MicroRNA-199a in BMSC-secreted exosomes showed a superior protective role against ECM degradation by targeting GREM1 to inactivate the TGF-βpathway.…”

Section: Impacts Of Msc-derived Exosomes On Ivddmentioning

confidence: 98%

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Mesenchymal Stem Cell-Derived Exosomes as a Novel Strategy for the Treatment of Intervertebral Disc Degeneration

Gao

et al. 2022

Front. Cell Dev. Biol.

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Intervertebral disc degeneration (IVDD) has been reported to be the most prevalent contributor to low back pain, posing a significant strain on the healthcare systems on a global scale. Currently, there are no approved therapies available for the prevention of the progressive degeneration of intervertebral disc (IVD); however, emerging regenerative strategies that aim to restore the normal structure of the disc have been fundamentally promising. In the last decade, mesenchymal stem cells (MSCs) have received a significant deal of interest for the treatment of IVDD due to their differentiation potential, immunoregulatory capabilities, and capability to be cultured and regulated in a favorable environment. Recent investigations show that the pleiotropic impacts of MSCs are regulated by the production of soluble paracrine factors. Exosomes play an important role in regulating such effects. In this review, we have summarized the current treatments for disc degenerative diseases and their limitations and highlighted the therapeutic role and its underlying mechanism of MSC-derived exosomes in IVDD, as well as the possible future developments for exosomes.

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Section: Impacts Of Msc-derived Exosomes On Ivddmentioning

confidence: 85%

Section: Impacts Of Msc-derived Exosomes On Ivddmentioning

confidence: 98%

Mesenchymal Stem Cell-Derived Exosomes as a Novel Strategy for the Treatment of Intervertebral Disc Degeneration

Gao

et al. 2022

Front. Cell Dev. Biol.

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“…[122] Other studies provide additional evidence that substantiate the therapeutic potential of stem cell-derived EVs in mouse and rabbit models, where EV treatment led to a reduction in NPC necrosis and apoptosis, decreased catabolic enzyme and proinflammatory cytokine production, increased GAG content, and improvements in gait pattern, disc height index, MRI signal intensity, and histological score. [99,104,109,120,121,123,124] Some studies attribute these therapeutic effects to specific miRs found in EVs, where Cheng et al highlighted the role of miR-21 in preventing apoptosis, Zhang et al elucidated the role of miR-410 in reducing pyroptosis, and Xie et al specified the protective role of miR-31-5p in the ATF6/(ER stress pathway. [104,122,124] Conversely, other studies attribute therapeutic effects to a downregulation of specific miRs, where Yuan et al used MSC-EVs to deliver AntagomiR-4450 and block miR-4450, which in turn alleviated IVDD.…”

Section: Stem Cell-derived Evs Decelerate Ivdd In Vivomentioning

confidence: 99%

Extracellular Vesicles as an Emerging Treatment Option for Intervertebral Disc Degeneration: Therapeutic Potential, Translational Pathways, and Regulatory Considerations

DiStefano

Vaso

Danias

et al. 2021

Adv Healthcare Materials

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Emergent approaches in regenerative medicine look toward the use of extracellular vesicles (EVs) as a next-generation treatment strategy for intervertebral disc (IVD) degeneration (IVDD) because of their ability to attenuate chronic inflammation, reduce apoptosis, and stimulate proliferation in a number of tissue systems. Yet, there are no Food and Drug Administration (FDA)-approved EV therapeutics in the market with an indication for IVDD, which motivates this article to review the current state of the field and provide an IVD-specific framework to assess its efficacy. In this systematic review, 29 preclinical studies that investigate EVs in relation to the IVD are identified, and additionally, the regulatory approval process is reviewed in an effort to accelerate emerging EV-based therapeutics toward FDA submission and timeline-to-market. The majority of studies focus on nucleus pulposus responses to EV treatment, where the main findings show that stem cell-derived EVs can decelerate the progression of IVDD on the molecular, cellular, and organ level. The findings also highlight the importance of the EV parent cell's pathophysiological and differentiation state, which affects downstream treatment responses and therapeutic outcomes. This systematic review substantiates the use of EVs as a promising cell-free strategy to treat IVDD and enhance endogenous repair.

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“…The upregulation of miR-142-3p or miR-199 delivered by MSC-derived exosomes may protect NPC from injury through inhibition of mitogen-activated protein kinase (MAPK) signaling [132,133]. In addition, miR-199a decreased MMP-2, MMP-6, TIMP-1 and apoptotic cells in a mouse model of IDD, while the expression of collagen type II, aggrecan, increased following the exposition to BMSC EVs in vitro [134]. Among other miRNAs previously identified, miR-27a was involved in the regulation of apoptotic pathways and in the prevention of IDD through the ability to suppress ECM degradation targeting MMP-13 [135,136].…”

Section: The Role Of Mirnas In Iddmentioning

confidence: 99%

Mesenchymal Stem Cell-Derived Exosomes: The New Frontier for the Treatment of Intervertebral Disc Degeneration

et al. 2021

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Low back pain (LBP) is one of the most frequent symptoms associated with intervertebral disc degeneration (IDD) and affects more than 80% of the population, with strong psychosocial and economic impacts. The main cause of IDD is a reduction in the proteoglycan content within the nucleus pulposus (NP), eventually leading to the loss of disc hydration, microarchitecture, biochemical and mechanical properties. The use of mesenchymal stem cells (MSCs) has recently arisen as a promising therapy for IDD. According to numerous reports, MSCs mediate their regenerative and immunomodulatory effects mainly through paracrine mechanisms. Recent studies have suggested that extracellular vesicles (EVs) extracted from MSCs may be a promising alternative to cell therapy in regenerative medicine. EVs, including exosomes and microvesicles, are secreted by almost all cell types and have a fundamental role in intercellular communication. Early results have demonstrated the therapeutic potential of MSCs-derived EVs for the treatment of IDD through the promotion of tissue regeneration, cell proliferation, reduction in apoptosis and modulation of the inflammatory response. The aim of this review is to focus on the biological properties, function, and regulatory properties of different signaling pathways of MSCs-derived exosomes, highlighting their potential applicability as an alternative cell-free therapy for IDD.

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Bone mesenchymal stem cell-derived extracellular vesicles promote the repair of intervertebral disc degeneration by transferring microRNA-199a

Cited by 39 publications

References 41 publications

Mesenchymal Stem Cell-Derived Exosomes as a Novel Strategy for the Treatment of Intervertebral Disc Degeneration

Mesenchymal Stem Cell-Derived Exosomes as a Novel Strategy for the Treatment of Intervertebral Disc Degeneration

Extracellular Vesicles as an Emerging Treatment Option for Intervertebral Disc Degeneration: Therapeutic Potential, Translational Pathways, and Regulatory Considerations

Mesenchymal Stem Cell-Derived Exosomes: The New Frontier for the Treatment of Intervertebral Disc Degeneration

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