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3D-ASC-Exos as a novel drug carrier for glioma treatment

ABSTRACT: It is known that antler stem cell extract has an inhibitory effect on glioma growth. Therefore, it is speculated that antler stem cell-derived exosomes (ASC-Exos) can be used as a new drug carrier for the treatment of glioma. Due to the limitation of exosome sources, we constructed a 3D culture system to harvest more exosomes. In this experiment, compared with the 2D-ASC-Exos obtained from the traditional 2D culture, the 3D-ASC-Exos obtained from our constructed 3D culture system were concentrated nearly 30 times in the culture medium volume, which was more convenient for subsequent purification. The two forms of ASC-Exos had similar morphologies and surface markers, but 3D-ASC-Exos were enriched with more miRNAs related to tumor suppression. In vitro experiments demonstrated that 3D-ASC-exosomes loaded with temozolomide (TMZ) inhibited the proliferation, migration and invasion abilities of glioma cells and promoted the apoptosis of glioma cells. The vivo tumor-bearing mouse model demonstrated that 3D-ASC-Exos loaded with TMZ exerted tumor-suppressive effects by inhibiting tumor growth and promoting tumor apoptosis. Meanwhile, the treatment with 3D-ASC-Exos loaded with TMZ caused no damage to the various tissues and organs of mice compared with the TMZ group. In conclusion, 3D-ASC-Exos can be used as a novel drug carrier for the treatment of glioma.

ORGANISM(S): Cervus nippon

PROVIDER: GSE305022 | GEO | 2025/12/02

REPOSITORIES: GEO

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Project description:Osteoarthritis (OA) is a progressive degenerative joint disorder characterized by chondrocyte dysfunction and extracellular matrix degradation. While stem cell therapies have been constrained by immunological rejection risks, their derived extracellular vesicles (Exos) emerge as a promising alternative therapeutic approach. Antler, a remarkable regenerative organ with extraordinary regenerative capacity and chondrogenic potential, offers a unique biological resource. Antler Stem Cells (ASCs) provide an innovative extracellular vesicle source (ASC-Exos) that presents a compelling therapeutic strategy for addressing OA's complex pathogenesis. To investigate the therapeutic effects and mechanism of ASC-Exos in OA treatment. ASCs characteristics were confirmed through immunofluorescence and tri-lineage differentiation, while exosomes were validated using transmission electron microscopy, nanoparticle tracking analysis, and Western blot. A rat OA model was established to evaluate therapeutic effects of ASC-Exos via different administration routes. Small RNA sequencing identified key extracellular vesicle components, while dual-luciferase reporter assays confirmed regulatory interactions between miR-140 and metalloproteinase-13(MMP13). Stable miR-140 overexpressing ASCs were generated through lentiviral transduction. An IL-1β-stimulated chondrocyte OA model was employed to assess the impact of miR-140-engineered ASC-Exos (miR-140-Exos) on cellular proliferation, migration, and apoptosis. The therapeutic potential was further evaluated in in vivo animal models. We successfully isolated and characterized ASCs and ASC-Exos. Intra-articular injection of ASC-Exos demonstrated superior cartilage repair efficacy. The critical extracellular vesicle component miR-140 was identified. In vitro studies revealed that miR-140-Exos significantly enhanced chondrocyte proliferation and migration while reducing cellular apoptosis. Dual-luciferase assays confirmed miR-140 directly targets MMP13, with MMP13 overexpression partially reversing miR-140-mediated cellular effects. In vivo investigations demonstrated that miR-140-modified ASC-Exos effectively inhibited COL II degradation and suppressed NLRP3 elevation, thereby providing anti-inflammatory benefits and promoting cartilage regeneration. miR-140-Exos represent an innovative therapeutic approach for osteoarthritis, effectively promoting cartilage regeneration and alleviating inflammation through MMP13 inhibition, presenting a novel therapeutic strategy for OA treatment.

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3D-ASC-Exos as a novel drug carrier for glioma treatment

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