Mesenchymal stem cell-derived exosomes ameliorate intervertebral disc degeneration via anti-oxidant and anti-inflammatory effects

Chen, Xia; Zeng, Zhu; Fang, Bin; Tao, Min; Gu, Chenhui; Zheng, Lin; Wang, Yiyun; Shi, Yiling; Chen, Fang; Mei, Sheng; Chen, Qi; Zhao, Juanjuan; Lin, Xianfeng; Fan, Shunwu; Jin, Yongming; Chen, Pengfei

doi:10.1016/j.freeradbiomed.2019.07.026

Cited by 223 publications

(209 citation statements)

References 53 publications

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“…Although not yet investigated in the IVD, NLRP3 inflammasome activity is known to be controlled by miR-223 (Bauernfeind et al, 2012). Importantly, the positive effects of EVs were not restricted to in vitro conditions but could also be replicated in a rabbit IVD degeneration model (Xia et al, 2019). Whether MSC-derived EVs may also affect the phenotype of invaded macrophages in the IVD and thus cause a shift from an inflammatory M1 toward a regenerative M2 phenotype is currently unclear, albeit initial data in that respect could be collected in skin (He et al, 2019).…”

Section: Modulating Inflammationmentioning

confidence: 96%

“…As chronic inflammation in the IVD arising from resident cells (and in the case of structural failure of the tissue also from invading immune cells) is associated with back pain development (Wuertz and Haglund, 2013;Johnson et al, 2015), many researchers consider the modulation of inflammation as therapeutically more relevant and achievable than inducing full regeneration. Following this strategy, Xia et al (2019) tested whether MSC-derived EVs can reduce H 2 O 2 -induced inflammation in NP cells. Results of this study provide compelling evidence for anti-inflammatory properties of EVs via modulation of the NLRP3 inflammasome and through restoration of damaged mitochondria (Xia et al, 2019).…”

Section: Modulating Inflammationmentioning

confidence: 99%

“…Following this strategy, Xia et al (2019) tested whether MSC-derived EVs can reduce H 2 O 2 -induced inflammation in NP cells. Results of this study provide compelling evidence for anti-inflammatory properties of EVs via modulation of the NLRP3 inflammasome and through restoration of damaged mitochondria (Xia et al, 2019).…”

Section: Modulating Inflammationmentioning

confidence: 99%

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Therapeutic Potential of Extracellular Vesicles in Degenerative Diseases of the Intervertebral Disc

Piazza

Dehghani

Gaborski

et al. 2020

Front. Bioeng. Biotechnol.

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Extracellular vesicles (EVs) are lipid membrane particles carrying proteins, lipids, DNA, and various types of RNA that are involved in intercellular communication. EVs derived from mesenchymal stem cells (MSCs) have been investigated extensively in many different fields due to their crucial role as regeneration drivers, but research for their use in degenerative diseases of the intervertebral disc (IVD) has only started recently. MSC-derived EVs not only promote extracellular matrix synthesis and proliferation in IVD cells, but also reduce apoptosis and inflammation, hence having multifunctional beneficial effects that seem to be mediated by specific miRNAs (such as miR-233 and miR-21) within the EVs. Aside from MSC-derived EVs, IVD-derived EVs (e.g., stemming from notochordal cells) also have important functions in IVD health and disease. This article will summarize the current knowledge on MSC-derived and IVDderived EVs and will highlight areas of future research, including the isolation and analysis of EV subpopulations or exposure of MSCs to cues that may enhance the therapeutic potential of released EVs.

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Section: Modulating Inflammationmentioning

confidence: 96%

Section: Modulating Inflammationmentioning

confidence: 99%

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Therapeutic Potential of Extracellular Vesicles in Degenerative Diseases of the Intervertebral Disc

Piazza

Dehghani

Gaborski

et al. 2020

Front. Bioeng. Biotechnol.

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“…This increased production of ECM may account for the suppressed MMP-1 production by the DCs as the ECM provided the DCs with favorable environment. Exosomes derived from hMSCs were also reported to suppress H 2 O 2 -induced NP cell in ammation [29]. This means that sEVs were able to assist the DCs to rebalance homeostasis in this 3D model.…”

Section: Discussionmentioning

confidence: 62%

Extracellular vesicles from human mesenchymal stem cells expedite chondrogenesis in 3D human degenerative disc cell cultures

Hingert

Ekström

Aldridge

et al. 2020

Preprint

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Abstract Background: Extracellular vesicles (EVs) from human mesenchymal stem cells (hMSCs) are known to be mediators of intercellular communication and has been suggested as possible therapeutic agents in many diseases. Their potential use in intervertebral disc (IVD) degeneration associated with low back pain (LBP) is yet to be explored. Since LBP affects more than 85% of the western population resulting in high socioeconomic consequences there is a demand for exploring new and possibly mini-invasive treatment alternatives. In this study, the effect of hMSCs derived small EVs (sEVs) on degenerated disc cells (DCs) isolated from patients with degenerative discs and chronic LBP was investigated in a 3D in vitro model. Methods: hMSCs were isolated from bone marrow aspirate and EVs were isolated from conditioned media of the hMSCs by differential centrifugation and filtration. 3D pellet cultures of DCs were stimulated with the EVs at 5x1010 vesicles/mL concentration for 28 days and compared to control. The pellets were harvested at day 7, 14, and 28 and evaluated for cell proliferation, viability, ECM production, apoptotic activity, chondrogenesis and cytokine secretions.Results: The findings demonstrated that treatment with sEVs from hMSCs resulted in more than 50% increase in cell proliferation and decrease in cellular apoptosis in degenerated DCs from this patient group. ECM production was also observed as early as in day 7 and was more than three times higher in the sEVs treated DC pellets compared to control cultures. Further, sEVs treatment suppressed secretion of MMP-1 in the DCs. Conclusion: hMSC derived sEVs improved cell viability and expedited chondrogenesis in DCs from degenerated IVDs. These findings open up for new tissue regeneration treatment strategies to be developed for degenerative disorders of the spine.

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“…Exosomes are extracellular vesicles with diameters of 30-150 nm. After being released from cells, such as liver cells, MSCs, and tumor cells, exosomes transport membrane components, proteins, microRNAs and mRNAs into the intracellular environment upon fusion with the cytoplasmic membrane [11,12] and then exert therapeutic effects on liver ischemia-reperfusion injury and degenerative diseases through cellto-cell communication, cell signaling and metabolism modulation [13][14][15]. Researches showed that in ammation and degeneration of CEP could accelerate IVDD, but IVDD are thought to be repaired via conversion normal CESCs into NPCs or by strengthening the nutrient supply of intervertebral discs via normal CEP [5,16].…”

Section: Introductionmentioning

confidence: 99%

Exosomes from normal cartilage endplate stem cells ameliorate intervertebral disc degeneration more effectively than exosomes from degenerated cartilage endplate stem cell by activating the AKT/autophagy pathway

Luo

Jian

Sun³

et al. 2020

Preprint

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Background Nucleus pulposus cells (NPCs) apoptosis is an important factor in exacerbating intervertebral disc degeneration (IVDD) that can be effectively suppressed by exosomes. The aim of this study was to reaearch whether normal cartilage endplate stem cells (CESCs) derived exosomes (N-Exos) were more conducive to activation of autophagy and inhibition of NPCs apoptosis and IVDD than degenerated CESCs derived exosomes (D-Exos) or not. Methods Rat CESCs were isolated and identified, and the exosomes produced by normal CESCs and degenerated CESCs were extracted. The bioinformatics differences between normal CESCs derived exosomes (N-Exos) and degenerated CESCs derived exosome (D-Exos) were analyzed by mass spectrometry, heat map and KEGG enrichment analysis biology. The effects of N-Exos and D-Exos on the inhibition of NPCs apoptosis were examined by TUNEL staining, flow cytometry and western blotting. The involvement of the AKT and autophagy signaling pathways was investigated using the signaling inhibitor LY294002. Magnetic resonance imaging, western blotting and immunofluorescence staining were used to evaluate the therapeutic effects of N-Exos in vivo. Results CESCs in the cartilage endplate (CEP) could secrete a large amount of exosomes. N-Exos were more conducive to activation of autophagy than D-Exos. The apoptotic rate of NPCs was decreased obviously after treatment with N-Exos than after D-Exos treatment. N-Exos inhibited NPCs apoptosis or attenuated IVDD in a rat tail model by activating the AKT and autophagy signaling pathways. Conclusions It was the first to confirm that CEP could delay the progression of IVDD through exosomes secreted by normal CESCs. The therapeutic effects of N-Exos on inhibiting NPCs apoptosis and slowing IVDD progression was more effective than D-Exos by activating the PI3K/AKT/autophagy pathway, which explained the reason that the incidence of IVDD was increased after inflammation of the CEP.

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Mesenchymal stem cell-derived exosomes ameliorate intervertebral disc degeneration via anti-oxidant and anti-inflammatory effects

Cited by 223 publications

References 53 publications

Therapeutic Potential of Extracellular Vesicles in Degenerative Diseases of the Intervertebral Disc

Therapeutic Potential of Extracellular Vesicles in Degenerative Diseases of the Intervertebral Disc

Extracellular vesicles from human mesenchymal stem cells expedite chondrogenesis in 3D human degenerative disc cell cultures

Exosomes from normal cartilage endplate stem cells ameliorate intervertebral disc degeneration more effectively than exosomes from degenerated cartilage endplate stem cell by activating the AKT/autophagy pathway

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