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Characterization of Urine Stem Cell-Derived Extracellular Vesicles Reveals B Cell Stimulating Cargo.

ABSTRACT: Elucidation of the biological functions of extracellular vesicles (EVs) and their potential roles in physiological and pathological processes is an expanding field of research. In this study, we characterized USC-derived EVs and studied their capacity to modulate the human immune response in vitro. We found that the USC-derived EVs are a heterogeneous population, ranging in size from that of micro-vesicles (150 nm-1 ?m) down to that of exosomes (60-150 nm). Regarding their immunomodulatory functions, we found that upon isolation, the EVs (60-150 nm) induced B cell proliferation and IgM antibody secretion. Analysis of the EV contents unexpectedly revealed the presence of BAFF, APRIL, IL-6, and CD40L, all known to play a central role in B cell stimulation, differentiation, and humoral immunity. In regard to their effect on T cell functions, they resembled the function of mesenchymal stem cell (MSC)-derived EVs previously described, suppressing T cell response to activation. The finding that USC-derived EVs transport a potent bioactive cargo opens the door to a novel therapeutic avenue for boosting B cell responses in immunodeficiency or cancer.

SUBMITTER: Zidan AA

PROVIDER: S-EPMC7796485 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature

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Characterization of Urine Stem Cell-Derived Extracellular Vesicles Reveals B Cell Stimulating Cargo.

Zidan Asmaa A AA Al-Hawwas Mohammed M Perkins Griffith B GB Mourad Ghada M GM Stapledon Catherine J M CJM Bobrovskaya Larisa L Zhou Xin-Fu XF Hurtado Plinio R PR

International journal of molecular sciences 20210105 1

Elucidation of the biological functions of extracellular vesicles (EVs) and their potential roles in physiological and pathological processes is an expanding field of research. In this study, we characterized USC-derived EVs and studied their capacity to modulate the human immune response in vitro. We found that the USC-derived EVs are a heterogeneous population, ranging in size from that of micro-vesicles (150 nm-1 μm) down to that of exosomes (60-150 nm). Regarding their immunomodulatory funct ...[more]

PMID: 33466423

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Project description:BackgroundGrowing evidence has suggested the role of stem cell-derived small extracellular vesicles (sEVs) in intervertebral disc degeneration (IVDD). The cargo sorting of sEVs, particularly miRNAs, may be influenced when the donor cell is subjected to oxidative stress. Here, we discovered that miRNAs containing specific motifs are selectively sorted into intraluminal vesicles within mesenchymal stem cells (MSCs) in response to oxidative stress.MethodsAnalysis of miRNA cargoes in sEVs derived from normal MSCs (C-sEVs) or stressed MSCs (T-sEVs) was conducted using miRNA sequencing. Differential expressed miRNAs in sEVs and the identification of motifs were evaluated through bioinformatics analysis. Protein binding was assessed using immunofluorescent staining and immunoprecipitation analysis. Additionally, RNA pull down and RNA immunoprecipitation (RIP) immunoprecipitation were employed to determine the binding between miRNAs and proteins. The effects of C-sEVs and T-sEVs on IVDD were compared by detecting the expression levels of phenotypic genes in vitro or histological evaluation in vivo.ResultsThe sorting process of miRNAs is mediated by the nucleocytoplasmic transport of heterogeneous nuclear ribonucleoproteins, which in turn facilitates the phosphorylation of SNAP25 and promotes the transport and secretion of sEVs. Additionally, CHMP1B plays a role in membrane repair and protects against cell ferroptosis upon oxidative stress, concurrently affecting the release of sEVs. Notably, stem cell-derived sEVs associated with ferroptosis impair the therapeutic efficacy for IVDD. However, the application of engineered sEVs containing a specific miRNA inhibitor exhibits the potential to reinstate the therapeutic efficacy for IVDD both in vitro and in vivo.ConclusionsTaken together, our findings shed light on the mechanism of miRNAs sorting into sEVs and offer new insights for the optimization of sEV-based treatments during intervertebral disc regeneration. regeneration.

Dataset Information

Characterization of Urine Stem Cell-Derived Extracellular Vesicles Reveals B Cell Stimulating Cargo.

Publications

Characterization of Urine Stem Cell-Derived Extracellular Vesicles Reveals B Cell Stimulating Cargo.

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