bims-engexo 2025-07-13 papers

Int Immunopharmacol. 2025 Jul 09. pii: S1567-5769(25)01160-9. [Epub ahead of print]162 115170

Engineered IFNγ-loaded exosomes reprogram macrophage polarization and suppress tumor cell proliferation in vitro.

Yun Chen, Zhuoling Du, Weiwei Jiang, Linghong Kong, Dan Huang, Changchun Zeng, Hanping Liu.

Macrophages are part of the immune system and play a complex role in the development of cancer. Tumor-associated macrophages (TAMs) exhibit dynamic plasticity between pro-tumorigenic (M2) and anti-tumorigenic (M1) phenotypes, presenting a promising therapeutic target for cancer immunotherapy. While pharmacological modulation of M2 to M1 repolarization shows therapeutic potential, current cytokine delivery strategies face critical challenges including non-specific macrophage clearance. To address these limitations, we developed an engineered exosome system (EXO-IFNγ) through efficient loading of interferon-γ (IFNγ) into THP-1 macrophage-derived exosomes. Functional investigations demonstrated that EXO-IFNγ effectively reprogrammed human peripheral blood mononuclear cells (PBMCs) derived M2 macrophages toward the M1 phenotype, exhibiting significantly superior polarization-modulating capacity compared to free IFNγ. To elucidate the therapeutic implications of phenotypic conversion, the bioactivity of conditioned medium (CM) derived from repolarized M1 macrophages was evaluated. The conditioned medium from repolarized M1 macrophages demonstrated potent tumor-suppressive activity, effectively inhibiting tumor cell growth and migration. Notably, the engineered exosomal delivery system demonstrated unique sustained payload release properties, endowing EXO-IFNγ generated CM with prolonged bioactivity compared to the CM produced by using IFNγ alone. Thus, EXO-IFNγ is a new macrophage polarization strategy to achieve good tumor cell killing effect by combining chemotherapy and immunotherapy.

Keywords: Engineered exosomes; Interferon-γ (IFNγ); Macrophage polarization

DOI: https://doi.org/10.1016/j.intimp.2025.115170

Front Cell Dev Biol. 2025 ;13 1621289

Mechanistic insights into adipose-derived stem cells and exosomes in ischemia-reperfusion injury repair: from shared pathways to organ-specific therapeutics.

Jiaqian Si, Jie Wang, Hao Dai, Tuochen Lv, Songyun Zhao, Wanying Chen, Liqun Li, Siqi Ding, Yucang He.

Ischemia-reperfusion injury (IRI) has become a significant challenge for clinical treatment due to the complex multi-mechanism pathological cascade response, including oxidative stress, inflammatory bursts, and programmed cell death. Adipose-derived stem cells (ADSCs) and their exosomes (ADSCs-exosomes) are emerging as a breakthrough therapeutic strategy to reverse IRI, owing to their multi-target synergistic effects. This review systematically analyzes the two major repair modes of ADSCs and ADSCs-exosomes: the "common protection" mechanism, which includes anti-inflammatory, anti-oxidative, and anti-apoptotic effects through paracrine regulation of miRNAs targeting the NF-κB/NRF2/β-catenin signaling axis; and precision repair, which is achieved through organ-specific targets, including hepatic mitochondrial dynamics and pyroptosis inhibition, cardiac macrophage polarization and neutrophil clearance, renal anti-fibrosis and erythropoietin (EPO) activation, as well as brain iron death regulation and microglial remodeling. From the perspective of the mechanism interaction network, this paper first proposes a theoretical framework of "multi-organ shared core pathways and dynamic regulation of different targets." It also reviews the translational potential of combined therapeutic strategies based on engineered exosomes delivery systems and biomaterials, emphasizing the optimization of delivery efficiency and functional enhancement to address the bottleneck of clinical applications. The ADSCs-mediated IRI intervention system provides an essential theoretical and technical basis for the development of individualized precision therapies.

Keywords: adipose-derived stem cells; exosomes; ischemia-reperfusion injury; multimechanism synergy; therapeutic strategy

DOI: https://doi.org/10.3389/fcell.2025.1621289

Curr Top Med Chem. 2025 Jul 09.

Exosome-Mediated Strategies for Melanoma Eradication: A Comprehensive Review.

Lalit Kumar, Ritesh Rana, Isha Singh, Sumit Kumar, Vikas Aggarwal, Komal Komal, Vuluchala Jyothiraditya.

INTRODUCTION: Exosomes, which are vesicles that are naturally derived and contain a biomolecular payload, are promising vehicles for melanoma therapy because of their biocompatibility, targeting capabilities, and stability. This review emphasizes their capacity to circumvent the constraints of conventional treatments.
METHODS: We carried out a comprehensive search of PubMed, ScienceDirect, and Google Scholar for peer-reviewed articles published between 2015 and 2024 utilizing terms such as "exosomes," "melanoma," and "chemotherapy." Studies on exosome characterization or non-melanoma malignancies were excluded from the inclusion criteria, which centered on exosome-based therapeutics.
RESULTS: Drugs delivered via exosomes, such as small interfering RNA (siRNA) and chemotherapeutics, demonstrated enhanced tumor accumulation, achieving 2.5 times greater bioavailability and resulting in a tumor reduction of 60 to 90% when compared to their free counterparts. Surface modifications, such as cRGD peptides, have been shown to enhance targeting capabilities, whereas exosome-mediated photodynamic therapy has been effective in augmenting reactive oxygen species generation and promoting apoptosis.
DISCUSSION: Exosomes tackle significant challenges such as drug resistance and systemic toxicity; however, they encounter obstacles related to scalability and immunogenicity. Their dual function in tumor advancement and treatment highlights the necessity for standardized protocols.
CONCLUSION: Exosome-based therapies signify a groundbreaking advancement in the treatment of melanoma. Future endeavors should refine engineering methodologies, enhance production capabilities, and substantiate effectiveness through rigorous clinical trials.

Keywords: Chemotherapy; Exosomes; Melanoma; Photodynamic therapy; Small interfering RNA

DOI: https://doi.org/10.2174/0115680266373170250624095758

Front Pharmacol. 2025 ;16 1617874

The role of synovial mesenchymal stem cell-derived exosomes in cartilage repair: a systematic review.

Jiemao Su, Yansong Qi, Lin Niu, Yongxiang Wang, Baogang Wei, Bingxian Ma, Keyu Kong, Zanjing Zhai, Yongsheng Xu.

Background: Knee osteoarthritis (KOA) is the most widespread degenerative disease in the cumulative population. With the increasing aging of the population, KOA has become one of the most important factors leading to joint deformities in middle-aged and elderly people. At present, the therapeutic effect of synovial mesenchymal stem cells (SMSCs) has gradually attracted the attention of many researchers. Due to their better chondrogenic ability, they have gradually become an effective way to treat cartilage injury. Because its function mainly relies on exosomes and exosomes have many advantages of cell-free therapy, it has attracted much attention from researchers.
Methods: The study was searched between April 20, 2014, and April 20, 2025, on China National Knowledge Infrastructure (CNKI), Wanfang database, PubMed, the Cochrane Library, and Web of Science. Two researchers independently reviewed the literature, extracted data, evaluated bias. In cases of disagreement, a third reviewer made the final decision.
Results: The initial literature search identified 198 potentially relevant studies. After removing 7 duplicate publications, 183 records remained for screening. Title and abstract review excluded 164 irrelevant studies. Full-text assessment was performed on the remaining 19 articles, of which 12 ultimately qualified for inclusion. Overall, the risk of bias in most of the eligible studies was unclear. In the 12 included studies, it was confirmed that SMSC-derived exosomes could maintain and promote cartilage repair and reduce the degree of cartilage damage by in vitro cell experiments. By isolating and extracting the main functional mirnas, it was found that these functional mirnas had a good therapeutic effect on cartilage injury.
Conclusion: SMSC-derived exosomes demonstrate significant potential for cartilage repair in KOA, primarily mediated by functional miRNAs. While in vitro results are promising, the unclear risk of bias in current studies underscores the need for higher-quality clinical research to validate their therapeutic application.
Systematic Review Registration: identifier [CRD420250651715].

Keywords: cartilage; exosomes; knee; mesenchymal stem cells; osteoarthritis; synovial

DOI: https://doi.org/10.3389/fphar.2025.1617874

Clin Transl Med. 2025 Jul;15(7): e70389

MiRNA-501-3p and MiRNA-502-3p: A promising biomarker panel for Alzheimer's disease.

Davin Devara, Bhupender Sharma, Gunjan Goyal, Daniela Rodarte, Aditi Kulkarni, Nathan Tinu, Ayana Pai, Subodh Kumar.

INTRODUCTION: Alzheimer's disease (AD) lacks a less invasive and early detectable biomarker. Here, we investigated the biomarker potential of miR-501-3p and miR-502-3p using different AD sources.
METHODS: MiR-501-3p and miR-502-3p expressions were evaluated in AD cerebrospinal fluid (CSF) exosomes, serum exosomes, familial and sporadic AD fibroblasts and B-lymphocytes by qRT-PCR analysis. Further, miR-501-3p and miR-502-3p expressions were analysed in APP, Tau plasmid transfected cells media exosomes and in different brain cell types.
RESULTS: MiR-501-3p and miR-502-3p expressions were significantly up-regulated in AD CSF exosomes relative to controls. MiRNA levels were high in accordance with amyloid plaque and NFT density in multiple brain regions. Similarly, both miRNAs were elevated in AD and MCI serum exosomes compared with controls. MiR-502-3p expression was high in familial AD and sporadic AD B-lymphocytes. MiR-501-3p and miR-502-3p expression were elevated intracellularly and secreted extracellularly in response to APP and Tau pathology. Finally, neurons and astrocytes displayed high expression of these miRNAs.
DISCUSSION: These results suggest that miR-501-3p and miR-502-3p could be promising biomarkers for AD.
KEY POINTS: MiR-501-3p and miR-502-3p expression is elevated in AD CSF exosomes, AD serum exosomes, AD B-lymphocytes and Aβ- and Tau-treated cells. MiR-501-3p and miR-502-3p are correlated with amyloid plaque and NFT tangle density in specific brain regions. MiR-501-3p and miR-502-3p are highly expressed in neurons and astrocytes, suggesting that these cells are the source of miRNA secretion. MiR-501-3p and miR-502-3p could be a promising biomarker panel for AD.

Keywords: Alzheimer's disease; CSF; MiR‐501‐3p; MiR‐502‐3p; biomarker; serum

DOI: https://doi.org/10.1002/ctm2.70389