bims-engexo 2025-08-17 papers

bims-engexo

Biomed News

on Engineered exosomes

Issue of 2025–08–17
nine papers selected by
Ravindran Jaganathan, Universiti Kuala Lumpur

Adipose-Derived Exosomes: mediators of crosstalk between Adipose tissue and cancer.
Self-healing injectable oxidized xanthan gum hydrogel loaded with exosomes and matrine modifies the microenvironment to promote diabetic wound healing.
Preparation and Characterization of Cyperus-Derived Exosomes Loaded with Selenium Nanoparticles for Selenium Delivery Based on Exosome Protein Quantitation.
Plasma Exosomal miR-17-5p Regulates Macrophage Polarization by Targeting Bcl11b in Sepsis-Induced Lung Injury.
Exosomal LncRNA SCAMP1-AS1 enhances osteosarcoma malignancy by regulating the LKB1-AMPK signaling pathway.
Astrocytes promote oligodendrocyte precursor cell proliferation via Cx47-mediated regulation of exosome-derived CHI3L1 secretion.
Potential Roles of Extracellular Vesicles in Murine Tear Fluids in the Physiology of Corneal Epithelial Cells In Vitro.
Harnessing Exosome-Based Drug Delivery for the Management of Pregnancy-Related Disorders: A New Frontier in Obstetric Therapeutics.
Human Amniotic Epithelial Stem Cell Exosomes Regulate Chondrocyte Ferroptosis through ACTA2-AS1-Targeted Binding to ACSL4 for Osteoarthritis Intervention.

Cancer Biol Ther. 2025 Dec;26(1): 2547564

Adipose-Derived Exosomes: mediators of crosstalk between Adipose tissue and cancer.

Changjian Wang, Zhikun Zheng, Chuangyan Wu, Dan Zhang, Yangchenxi Wang, Sheng Zhang, Geng Wang, Rui Zhou.

  Adipose-derived exosomes (ADEs), a subtype of extracellular vesicles, are critical mediators of communication between adipose tissue and tumors, playing pivotal roles in cancer progression and therapeutic response. These nanoscale vesicles carry microRNAs, proteins, and lipids that influence tumor cell proliferation, migration, metastasis, and immune modulation. The dual functions of ADEs - both in promoting and suppressing tumorigenesis - are largely dependent on their cellular origin, molecular cargo, and the characteristics of the tumor microenvironment. Recent studies have identified ADEs as potential diagnostic biomarkers, therapeutic targets, and drug delivery platforms, offering promising avenues for precision oncology. However, significant challenges - such as biological heterogeneity, lack of standardization in production, concerns regarding efficacy and safety, and regulatory constraints - continue to hinder their clinical translation. This review aimed to explore the multifaceted roles of ADEs in cancer pathogenesis, their therapeutic potential, and current limitations, providing insights to guide future research and clinical applications.

Keywords:  Adipose-derived exosomes; adipose tissue; cancer; exosome-based therapy; miRNA; tumor microenvironment

DOI:  https://doi.org/10.1080/15384047.2025.2547564
Int J Biol Macromol. 2025 Aug 08. pii: S0141-8130(25)07266-6. [Epub ahead of print]322(Pt 2): 146709

Self-healing injectable oxidized xanthan gum hydrogel loaded with exosomes and matrine modifies the microenvironment to promote diabetic wound healing.

Jincheng Du, Wei Hu, Juan Liu, Kai Gao.

  Diabetic wounds, as a severe chronic complication of diabetes mellitus associated with high morbidity and mortality rates, pose a significant burden on public healthcare systems. In this study, we developed an injectable self-healing hydrogel through reversible Schiff base covalent bonding between ε-polylysine hydrochloride (ε-PL) and oxidized xanthan gum (OXG). To enhance its biological functionality, we incorporated matrine (Mat) and exosomes (Exos) to create the composite EXEM (OXG/ε-PL/Exos/Mat) hydrogel, where ε-PL and Mat exhibited synergistic antibacterial effects while reducing drug-resistant infection risks. The encapsulated Exos effectively promoted wound neovascularization, regulated macrophage polarization, and attenuated persistent inflammation in diabetic wounds. These results demonstrate that the EXEM self-healing hydrogel can be injected to achieve complete wound coverage while simultaneously inhibiting bacterial growth, modulating inflammatory responses, and enhancing vascular regeneration, thereby improving the pathological microenvironment and accelerating diabetic wound healing with substantial research value and promising clinical translation potential.

Keywords:  Oxidized xanthan gum; Self-healing hydrogels; Ε-Polylysine hydrochloride

DOI:  https://doi.org/10.1016/j.ijbiomac.2025.146709
Foods. 2025 Aug 04. pii: 2724. [Epub ahead of print]14(15):

Preparation and Characterization of Cyperus-Derived Exosomes Loaded with Selenium Nanoparticles for Selenium Delivery Based on Exosome Protein Quantitation.

Dexiu Zhao, Xiaojun Yang, Abulimiti Kelimu, Bin Wu, Weicheng Hu, Hongbo Fan, Lei Jing, Dongmei Yang, Xinhong Huang.

  Appropriate carriers or templates are crucial for maintaining the stability, biological activity, and bioavailability of selenium nanoparticles (SeNPs). Selecting suitable templates remains challenging for fully utilizing SeNPs functionalities and developing applicable products. Exosome-like nanoparticles (ELNs) have gained importance in drug delivery systems, yet research on selenium products prepared using exosomes remains limited. To address this gap, we utilized Cyperus bean ELNs to deliver SeNPs, investigated three preparation methods for SeNPs-ELNs, identified the optimal approach, and performed characterization studies. Notably, all three methods successfully loaded SeNPs. Ultrasonic cell fragmentation is the optimal approach, achieving significant increases in selenium loading (5.59 ± 0.167 ng/μg), enlargement of particle size (431.17 ± 10.78 nm), and reduced absolute zeta potential (-4.1 ± 0.43 mV). Moreover, both exosome formulations demonstrated enhanced stability against aggregation during storage at 4 °C, while their stability varied with pH conditions. In vitro digestibility tests showed greater stability of SeNP-ELNs in digestive fluids compared to ELNs alone. Additionally, neither ELNs nor SeNP-ELNs exhibited cytotoxicity toward LO2 cells, and the relative erythrocyte hemolysis remained below 5% at protein concentrations of 2.5, 7.5, 15, 30, and 60 μg/mL. Overall, ultrasonic cell fragmentation effectively loaded plant-derived exosomes with nano-selenium at high capacity, presenting new opportunities for their use as functional components in food and pharmaceutical applications.

Keywords:  PEG precipitation; SeNPs; exosome; protein quantitation; ultrasonic cell fragmentation

DOI:  https://doi.org/10.3390/foods14152724
J Inflamm Res. 2025 ;18 10651-10668

Plasma Exosomal miR-17-5p Regulates Macrophage Polarization by Targeting Bcl11b in Sepsis-Induced Lung Injury.

Ying Xian, Yinfang Sun, Lifu Wang, Lin Lin, Zhongdao Wu, Kouxing Zhang, Rui Chen.

   Background: Sepsis is a life-threatening syndrome characterized by overwhelming inflammation and immune dysregulation, commonly complicated by acute lung injury. Patients with underlying conditions such as diabetes, malignancy, and chronic liver disease are particularly vulnerable. Dysregulated macrophage polarization plays a pivotal role in sepsis progression. Although exosomal microRNAs (miRNAs) have emerged as key immune modulators, the precise role of plasma-derived exosomal miR-17-5p in this process remains poorly defined. The transcription factor Bcl11b, previously linked to immune cell regulation, has not yet been studied in the context of sepsis-associated macrophage reprogramming.
Methods: Extracellular vehicles (EVs) were isolated from the plasma of sepsis patients and healthy controls. A series of in vitro and in vivo experiments were conducted to investigate the effect of exosomal miR-17-5p on macrophage polarization, using qRT-PCR, flow cytometry, ELISA, and Western blot analyses. Transcriptome sequencing and dual-luciferase reporter assays were used to explore the regulatory relationship between miR-17-5p and Bcl11b.
Results: Plasma exosomes derived from sepsis patients exhibited reduced levels of miR-17-5p and promoted M1 macrophage polarization, characterized by increased iNOS and pro-inflammatory cytokines. Overexpression of miR-17-5p inhibited M1 polarization and alleviated inflammatory injury both in LPS-treated macrophages and in a CLP-induced mouse model. Mechanistically, miR-17-5p directly targeted the 3'UTR of Bcl11b, suppressing its expression. Restoration of Bcl11b reversed the anti-inflammatory effects of miR-17-5p, reinforcing M1 polarization and exacerbating lung injury.
Conclusion: Plasma exosomal miR-17-5p promotes macrophage M1 polarization by targeting Bcl11b and contributes to sepsis-induced lung injury. These findings highlight a previously unrecognized miR-17-5p-Bcl11b regulatory axis and suggest a potential biomarker and therapeutic target for sepsis.

Keywords:  Bcl11b; acute lung injury; extracellular vesicles; macrophages polarization; miR-17-5p; sepsis

DOI:  https://doi.org/10.2147/JIR.S524742
Sci Rep. 2025 Aug 12. 15(1): 29560

Exosomal LncRNA SCAMP1-AS1 enhances osteosarcoma malignancy by regulating the LKB1-AMPK signaling pathway.

Yanxia Li, Xiuqi Zou, Xiaomin Feng, Jing Xia, Zhifeng Wu, Haili Ma.

  Exosomes are extracellular vesicles that facilitate communication among cells by exchanging signaling biomolecules with adjacent cells. Among the diverse signaling biomolecules, long noncoding RNAs (lncRNAs) can be selectively packaged into exosomes to influence cancer onset and progression through various mechanisms. This study aimed to explore the role of exosomal lncRNA SCAMP1-AS1 in osteosarcoma (OS). The expression of SCAMP1-AS1 was determined by quantitative reverse-transcription polymerase chain reaction in OS samples, and its role in OS was investigated by performing Cell Counting Kit-8, EdU, and Transwell assays. The characterization of exosomes derived from OS cell lines was conducted by transmission electron microscopyand Western blotting of CD9 and CD81. The effects of exosomes and exosomal SCAMP1-AS1 on OS cells were also evaluated in a series of cell assays. Furthermore, key molecules in the liver kinase B1-adenosine monophosphate-activated protein kinase (LKB1-AMPK) signaling pathway were analyzed by through Western blotting. The results revealed high SCAMP1-AS1 expression in OS, and its silencing in OS cells led to a reduction in cell proliferation, migration, and invasion. The OS cell-derived-exosomes increased the malignant characteristics in the target OS cell lines. Notably, exosomes obtained from OS cells in which SCAMP1-AS1 was silenced effectively counteracted the tumor-promoting effects typically observed with OS-derived exosomes on cocultured target OS cells by activating the LKB1-AMPK signaling pathway. These results demonstrate that exosomal SCAMP1-AS1 serves as a tumor promoter in OS by regulating the LKB1-AMPK signaling pathway.

Keywords:  Exosomes; LKB1-AMPK pathway; LncRNA SCAMP1-AS1; Osteosarcoma

DOI:  https://doi.org/10.1038/s41598-025-15125-2
Zhong Nan Da Xue Xue Bao Yi Xue Ban. 2025 Apr 28. pii: 1672-7347(2025)04-0573-13. [Epub ahead of print]50(4): 573-585

Astrocytes promote oligodendrocyte precursor cell proliferation via Cx47-mediated regulation of exosome-derived CHI3L1 secretion.

Xiaoyan Zhang, Nannan Cheng, Yan Peng.

   OBJECTIVES: Neurodegenerative diseases are closely associated with myelin loss, and the proliferation and differentiation of oligodendrocyte precursor cells (OPCs) are crucial to remyelination. However, the regulatory mechanisms involved remain incompletely understood. This study aims to investigate how astrocytes (ASTs) regulate the secretion of chitinase-3-like protein 1 (CHI3L1) via connexin 47 (Cx47)-mediated exosome signaling, and its subsequent effect on OPC proliferation.
METHODS: Primary cells were isolated from postnatal day 1 Sprague-Dawley (P1SD) rats to establish 3 culture conditions: OPCs alone (Group O), OPCs in direct contact with ASTs (Group C), and OPCs cultured with AST-conditioned medium (Group A). Cellular morphology and proliferation were assessed using optical microscopy, 5-ethynyl-2'- deoxyuridine (EdU) incorporation, and flow cytometry. RNA sequencing (RNA-Seq) and bioinformatics analysis (BA) were conducted to identify differentially expressed genes (DEGs) among groups. Protein expression and cell cycle distribution were analyzed by Western blotting (WB) and flow cytometry. Exosomes were isolated and purified via differential centrifugation, characterized by nanoparticle tracking analysis (NTA) and transmission electron microscopy (TEM), and CHI3L1 expression in exosomes was verified via WB. Cx47 was silenced using small interfering RNA (siRNA) to evaluate its effect on OPC proliferation and exosome secretion. Artificial exosomes were constructed by encapsulating CHI3L1 in single unilamellar vesicles (SUVs), whose structure and size were validated by NTA and TEM. Following Cx47 knockdown, artificial exosomes were added back, and OPC proliferation was assessed via flow cytometry and EdU assay.
RESULTS: Direct co-cultured with ASTs (Group C) resulted in significantly enhanced OPC proliferation compared to the Group O and Group A (P<0.05). RNA-Seq and WB analyses revealed that ASTs promote OPC proliferation and exosome secretion enriched in CHI3L1 through Cx47. Cx47 knockdown by siRNA led to significant decreases in OPC proliferation and exosome release (P<0.05). The inhibitory effect of Cx47 silencing on OPC proliferation was partially reversed by supplementation with either isolated exosomes or exogenous CHI3L1.
CONCLUSIONS: This study reveals a novel mechanism by which ASTs regulate OPC proliferation: Through direct contact, ASTs enhance the secretion of CHI3L1-rich exosomes via Cx47, thereby converting intercellular contact signals into secretory signals that promote OPC proliferation. As a key exosomal molecule, CHI3L1 may play an important role in neural function and remyelination and warrants further investigation.

Keywords:  5-ethynyl-2'-deoxyuridine; astrocytes; cell proliferation; chitinase-3-like protein 1; connexin 47; differentially expressed genes; exosomes; oligodendrocyte precursor cells; transcriptome sequencing

DOI:  https://doi.org/10.11817/j.issn.1672-7347.2025.240542
Int J Mol Sci. 2025 Aug 05. pii: 7559. [Epub ahead of print]26(15):

Potential Roles of Extracellular Vesicles in Murine Tear Fluids in the Physiology of Corneal Epithelial Cells In Vitro.

Saya Oya, Kazunari Higa, Tomohiro Yasutake, Risa Yamazaki-Hokama, Masatoshi Hirayama.

  Biological extracellular vesicles in tear fluids, such as exosomes, are thought to have physiological functions in the management of healthy ocular surface epithelium, including corneal epithelium. However, the physiological roles of tear extracellular vesicles in the ocular surface remain unclear. In this study, we investigated the physiological function of tear extracellular vesicles in mouse tear fluids in the ocular surface epithelium in vitro. Morphological analysis of the isolated extracellular vesicles from mouse tear fluids was performed using nanoparticle tracking analysis and transmission electron microscopy. The identified particles were characterised by immunoblotting for exosomal markers. After confirming the uptake of tear exosomes in cultured corneal epithelial cells, gene expression changes in mouse cultured corneal epithelial cells after tear exosome treatment were analysed. Immunostaining analysis was performed to confirm cell proliferation in the cultured corneal epithelial cells with tear exosome treatment. Tear fluids from mice contain nanoparticles with exosome-like morphologies, which express the representative exosomal markers CD9 and TSG101. The extracellular vesicles can be taken up by cultivated murine corneal epithelial cells in vitro and induce expression changes in genes related to the cell cycle, cell membranes, microtubules, and signal peptides. Treatment with the tear extracellular vesicles promoted cell proliferation of cultured murine corneal epithelial cells. Our study provides evidence that murine tear fluids contain extracellular vehicles like exosomes and they may contribute to the maintenance of the physiological homeostatic environment of the ocular surface.

Keywords:  corneal epithelium; dry eye disease; exosome; extracellular vesicles; tear fluid

DOI:  https://doi.org/10.3390/ijms26157559
J Drug Target. 2025 Aug 10. 1-30

Harnessing Exosome-Based Drug Delivery for the Management of Pregnancy-Related Disorders: A New Frontier in Obstetric Therapeutics.

Feihua Jin, Yaying Zhan, Shaomin Xu, Li Pan, Bingqing Chu, Jinghua Yu, Yupeng Wang, Wenli Xu, Zhimin Lu.

  Obstetric complications such as preeclampsia, preterm birth, and fetal growth restriction significantly impact maternal and neonatal health globally, contributing substantially to maternal and perinatal morbidity and mortality. These conditions often result in long-term health sequelae for affected offspring, including neurodevelopmental disorders, metabolic syndrome, and cardiovascular diseases. Despite advances in prenatal diagnostics and neonatal care, therapeutic options remain limited due to challenges imposed by the placental barrier, such as poor drug permeability, low bioavailability, and safety concerns. Exosomes, naturally occurring extracellular vesicles, offer promising solutions as targeted drug delivery systems due to their excellent biocompatibility, low immunogenicity, and ability to cross biological barriers. Specifically, exosomes are gaining recognition for their roles in maternal-fetal communication and immunological regulation, presenting potential both as biomarkers and therapeutic carriers in obstetric care. This review synthesizes current knowledge of exosome properties, their physiological and pathological roles in pregnancy, and explores their potential as innovative therapeutic delivery platforms. Additionally, the review addresses existing challenges in exosome technology, including production scalability, standardization, and safety, and outlines critical directions for future research and clinical translation.

Keywords:  Exosomes; drug delivery system; obstetric complications; placental barrier

DOI:  https://doi.org/10.1080/1061186X.2025.2546492
Research (Wash D C). 2025 ;8 0814

Human Amniotic Epithelial Stem Cell Exosomes Regulate Chondrocyte Ferroptosis through ACTA2-AS1-Targeted Binding to ACSL4 for Osteoarthritis Intervention.

Xiaofei Wang, Zhimin Wu, Lei Xu, Linbing Lou, Yuxia Yang, Jian Zhang, Haixiang Miao, Cunyi Xia, Zhiwei Peng, Dongsheng Yang, Zhiwen Tao, Xiangji Meng, Wenkang Liu, Meijuan Yuan, Jingcheng Wang, Wenyong Fei, Jihang Dai.

The inhibition of ferroptosis, a widespread form of nonapoptotic cell death, is considered a promising therapeutic approach for osteoarthritis (OA). Human amniotic epithelial stem cells (hAESCs) maintain multipotent differentiation potential, no tumorigenicity, low immunogenicity, and anti-inflammatory properties, rendering them highly biocompatible stem cells. Exosomes (Exo) are vesicular carriers for intercellular communication that participate importantly in regulating disease progression through paracrine signaling. In our study, under inflammatory stress conditions, actin alpha 2, smooth muscle antisense RNA1 (ACTA2-AS1) transcription was up-regulated in hAESCs, further delivered to chondrocytes via hAESC-derived Exo. Subsequently, ACTA2-AS1 could suppress ferroptosis in chondrocytes by facilitating the degradation of acyl-CoA synthetase long-chain family member 4 (ACSL4), a key regulator of ferroptosis, thereby modulating the progression of OA. In conclusion, for the first time, this study demonstrates the modulatory role of hAESC ACSL4 expression by releasing ACTA2-AS1-enriched Exo, leading to inhibited ferroptosis in chondrocytes and ultimately ameliorating OA progression. Thus, targeting Exo-mediated communication may offer novel therapeutic approaches for addressing OA linked to iron metabolism irregularities.

DOI: https://doi.org/10.34133/research.0814