Extracellular vesicle and soluble fractions of adipose tissue-derived mesenchymal stem cells secretome induce inflammatory cytokines modulation in an in vitro model of discogenic pain

González-Cubero, Elsa; González-Fernández, María Luisa; Olivera, Elı́as R.; Villar-Suárez, Vega

doi:10.1016/j.spinee.2022.01.012

Cited by 15 publications

(11 citation statements)

References 67 publications

(70 reference statements)

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“…The data in this study adds to the current literature supported by others [47] and positions the signi cant advantages of using the whole secretome compared with the EV populations in key aspects of the MSC regenerative spectrum thanks to its increased immunomodulation abilities and superior angiogenic properties.…”

Section: Discussionsupporting

confidence: 67%

Adipose stromal cells bioproducts as cell-free therapies: manufacturing and therapeutic dose determine in vitro functionality

Skovronova,

Scaccia,

Calcat-i-Cervera

et al. 2023

Preprint

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Background Extracellular vesicles (EV) are considered a cell-free alternative to mesenchymal stromal cell (MSC) therapy. Numerous reports describe the efficacy of EV in conferring immunomodulation and promoting angiogenesis, yet others report these activities to be conveyed in EV-free bioproducts. We hypothesized that this discrepancy may depend either on the method of isolation or rather the relative impact of the individual bioactive components within the MSC secretome. Methods To answer this question, we performed an inter-laboratory study evaluating EV generated from adipose stromal cells (ASC) by either sequential ultracentrifugation (UC) or size-exclusion chromatography (SEC). The effect of both EV preparations on immunomodulation and angiogenesis in vitro was compared to that of the whole secretome and of the EV-free protein fraction after SEC isolation. Results In the current study, neither the EV preparations, the secretome or the protein fraction were efficacious in inhibiting mitogen-driven T cell proliferation – highlighting the need for direct cell-to-cell contact. However, EV generated by SEC stimulated macrophage phagocytic activity to a similar extent as the secretome. In turn, tube formation and wound healing were strongly promoted by the ASC secretome and protein fraction, but not by EV. Within the secretome/protein fraction, VEGF was identified as a potential driver of angiogenesis, and was absent in both EV preparations. Conclusions Our data indicate that the effects of MSCs on immunomodulation and angiogenesis are EV-independent and rely on direct cell-to-cell contact or on the secretion of soluble factors, respectively. Specific MSC-EV effects need to be dissected for their use as cell-free therapeutics.

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Section: Discussionsupporting

confidence: 67%

Adipose stromal cells bioproducts as cell-free therapies: manufacturing and therapeutic dose determine in vitro functionality

Skovronova,

Scaccia,

Calcat-i-Cervera

et al. 2023

Preprint

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“…González-Cubero et al. showed that EVs and soluble fractions from conditioned media promote an in vitro anti-inflammatory modulation in intervertebral disc degeneration in a “highly synergistic way”, thus highlighting that the use of the whole secretome rather than isolated EVs might be more beneficial for therapy ( 21 ). While it is still hard to understand what exactly mediates the immunomodulatory potential, the effect might come from a synergistic combination of both the soluble factors from the secretome and the EVs.…”

Section: Multiparametric Influence On the Immunomodulatory Potential ...mentioning

confidence: 99%

Mesenchymal stromal cell derived extracellular vesicles as a therapeutic tool: immune regulation, MSC priming, and applications to SLE

Wong,

Stoilova,

Gazeau

et al. 2024

Front. Immunol.

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Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by a dysfunction of the immune system. Mesenchymal stromal cell (MSCs) derived extracellular vesicles (EVs) are nanometer-sized particles carrying a diverse range of bioactive molecules, such as proteins, miRNAs, and lipids. Despite the methodological disparities, recent works on MSC-EVs have highlighted their broad immunosuppressive effect, thus driving forwards the potential of MSC-EVs in the treatment of chronic diseases. Nonetheless, their mechanism of action is still unclear, and better understanding is needed for clinical application. Therefore, we describe in this review the diverse range of bioactive molecules mediating their immunomodulatory effect, the techniques and possibilities for enhancing their immune activity, and finally the potential application to SLE.

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“…It is hypothesized that obesity, especially abdominal obesity, exerts additional mechanical stress on the lower back, resulting in pain ( 59 ). In addition, adipose tissue can secrete pro-inflammatory cytokines, which could contribute to LBP ( 60 , 61 ). Accordingly, weight management may still offer benefits for LBP prevention and treatment.…”

Section: Discussionmentioning

confidence: 99%

Smoking and BMI mediate the causal effect of education on lower back pain: observational and Mendelian randomization analyses

Xu,

Qi,

Zhang

et al. 2024

Front. Endocrinol.

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ObjectiveLow back pain (LBP) has been associated with education in previous observational studies, but the causality remains unclear. This study aims to assess the impact of education on LBP and to explore mediation by multiple lifestyle factors.DesignUnivariable Mendelian randomization (MR) was performed to examine the overall effect of education on LBP. Subsequently, multivariable MR was conducted to assess both the direct effect of education on LBP and the influence of potential mediators. Indirect effects were estimated using either the coefficient product method or the difference method, and the proportion of mediation was calculated by dividing the indirect effect by the total effect. The observational study utilized data from the NHANES database collected between 1999 and 2004, and included 15,580 participants aged 20 years and above.ResultsIncreasing education by 4.2 years leads to a 48% reduction in the risk of LBP (OR=0.52; 95% CI: 0.46 to 0.59). Compared to individuals with less than a high school education, those with education beyond high school have a 28% lower risk of LBP (OR=0.72; 95% CI: 0.63 to 0.83). In the MR study, smoking accounts for 12.8% (95% CI: 1.04% to 20.8%) of the total effect, while BMI accounts for 5.9% (95% CI: 2.99% to 8.55%). The combined mediation effect of smoking and BMI is 27.6% (95% CI: 23.99% to 32.7%). In the NHANES study, only smoking exhibits a mediating effect, accounting for 34.3% (95% CI: 21.07% to 41.65%) of the effect, while BMI does not demonstrate a mediating role.ConclusionsHigher levels of education provide a protective effect against the risk of LBP. Additionally, implementing interventions to reduce smoking and promote weight loss among individuals with lower levels of education can also decrease this risk.

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Extracellular vesicle and soluble fractions of adipose tissue-derived mesenchymal stem cells secretome induce inflammatory cytokines modulation in an in vitro model of discogenic pain

Abstract: árez , Extracellular vesicle and soluble fractions of adipose tissue-derived mesenchymal stem cells secretome induce inflammatory cytokines modulation in an in vitro model of discogenic pain,

Cited by 15 publications

References 67 publications

Adipose stromal cells bioproducts as cell-free therapies: manufacturing and therapeutic dose determine in vitro functionality

Adipose stromal cells bioproducts as cell-free therapies: manufacturing and therapeutic dose determine in vitro functionality

Mesenchymal stromal cell derived extracellular vesicles as a therapeutic tool: immune regulation, MSC priming, and applications to SLE

Smoking and BMI mediate the causal effect of education on lower back pain: observational and Mendelian randomization analyses

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