Gastric cancer-derived exosomal let-7 g-5p mediated by SERPINE1 promotes macrophage M2 polarization and gastric cancer progression

Journal of Experimental & Clinical Cancer Research, Год журнала: 2025, Номер 44(1)

Опубликована: Янв. 2, 2025

Abstract Background Tumor-associated macrophages (TAMs), particularly M2-polarized TAMs, are significant contributors to tumor progression, immune evasion, and therapy resistance in gastric cancer (GC). Despite efforts target TAM recruitment or depletion, clinical efficacy remains limited. Consequently, the identification of targets that specifically inhibit reprogram TAMs presents a promising therapeutic strategy. Objective This study aims identify dual-function GC cells drives both malignant phenotypes M2 macrophage polarization, revealing its molecular mechanisms provide novel for selectivly targeting GC. Methods Transcriptomic data from adjacent tissues were utilized mRNAs associated with high infiltration poor prognosis. Single-cell sequencing elucidated cell types expressing gene. Transwell co-culture exosome intervention experiments demonstrated role polarization. Small RNA exosomes, western blotting, CoIP assays revealed underlying exosome-mediated Protein array, ChIP dual-luciferase reporter clarified by which gene regulated exosomal miRNA. In vivo validation was performed using xenograft models. Results SERPINE1 identified as highly expressed mRNA cells, significantly advanced stages, worse prognosis, higher patients overexpression promoted growth facilitated transfer let-7 g-5p via cancer-derived inducing Exosomal internalized downregulated SOCS7 protein levels, disrupting interaction STAT3 relieving inhibition phosphorylation, thereby leading hyperactivation, consequently drove Additionally, elevated expression activated JAK2, enhancing binding promoter promoting transcription, increasing levels exosomes. Conclusion cell-derived , functioning primary driver promotes polarization through regulation autocrine activation JAK2/STAT3 signaling pathway. These findings elucidate mechanism -induced highlight advancing immunotherapy targeted treatments

Язык: Английский

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Exosome-loaded methacrylated silk fibroin hydrogel delays intervertebral disc degeneration by DKK2-mediated mitochondrial unfolded protein response

Chemical Engineering Journal, Год журнала: 2025, Номер unknown, С. 162191 - 162191

Опубликована: Март 1, 2025

Язык: Английский

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Scalable production of anti-inflammatory exosomes from three-dimensional cultures of canine adipose-derived mesenchymal stem cells: production, stability, bioactivity, and safety assessment

BMC Veterinary Research, Год журнала: 2025, Номер 21(1)

Опубликована: Фев. 20, 2025

The therapeutic potential of exosomes derived from mesenchymal stem cells (MSCs) is increasingly recognized in veterinary medicine. This study explored the feasibility a microcarrier-based three-dimensional (3D) culture system for producing (cEXO). Investigations were conducted to enhance production efficiency, ensure stability, and evaluate cEXO anti-inflammatory applications while assessing their safety profile. 3D improved efficient cEXO, yielding with acceptable profiles, including size approximately 81.22 nm, negative surface charge, high particle concentration (1.32 × 109 particles/mL). Confocal imaging proved dynamic changes cell viability across phases, highlighting challenges maintaining during repeated exosome collection cycles. Characterization via transmission electron microscopy, nanoparticle tracking analysis, zeta-potential measurements confirmed stability functionality particularly when stored at -20 °C. Functional assays showed that exerted significant activity RAW264.7 macrophages an inverse dose-dependent manner, no observed cytotoxicity fibroblasts or macrophages. Acute toxicity testing rats revealed adverse effects on clinical parameters, organ health, body weight, supporting use. highlights scalable robust activity, profiles. These findings advance development cEXO-based therapies support application regenerative

Язык: Английский

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3D Culture of MSCs for Clinical Application

Bioengineering, Год журнала: 2024, Номер 11(12), С. 1199 - 1199

Опубликована: Ноя. 27, 2024

Mesenchymal stem cells (MSCs) play an important role in regenerative medicine and drug discovery due to their multipotential differentiation capabilities immunomodulatory effects. Compared with traditional 2D cultures of MSCs, 3D MSCs have emerged as effective approach enhance cell viability, proliferation, functionality, provide a more relevant physiological environment. Here, we review the therapeutic potential 3D-cultured highlighting roles tissue regeneration repair screening. We further summarize successful cases that apply modeling disease states, enabling identification novel strategies. Despite these promising applications, discuss challenges remain clinical translation MSC technologies, including stability, heterogeneity, regulatory issues. conclude by addressing obstacles emphasizing need for research fully exploit practice.

Язык: Английский

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Human embryonic stem cell spheroids derived exosomal hsa_circ_0003258 sequestered dual targeting of miR-502-5p on KLF4/NF-κB and GALNT4/P53 to mitigate inflammation and apoptosis in hepatic ischemia reperfusion injury

Chemical Engineering Journal, Год журнала: 2024, Номер unknown, С. 158068 - 158068

Опубликована: Ноя. 1, 2024

Язык: Английский

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Injectable biomimetic microcarriers harness synergistic effects of paracrine factors and cellular membranes to alleviate osteoarthritis

Chemical Engineering Journal, Год журнала: 2024, Номер 503, С. 158451 - 158451

Опубликована: Дек. 9, 2024

Язык: Английский

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