bims-engexo 2025-03-16 papers

bims-engexo

Biomed News

on Engineered exosomes

Issue of 2025–03–16
six papers selected by
Ravindran Jaganathan, Universiti Kuala Lumpur

Engineered exosomes restore miR-508-5p expression in uterine corpus endometrial carcinoma and reduce tumor progression and metastasis by targeting DLL3.
Harnessing miR-16-5p-Loaded Exosomes from Adipose-Derived Stem Cells to Restore Immune Homeostasis in SLE Patients.
Engineered extracellular vesicles promote the repair of acute kidney injury by modulating regulatory T cells and the immune microenvironment.
Exploring the role of exosomes in diabetic neuropathy: From molecular mechanisms to therapeutic potential.
Exosomes derived from baicalin‑pretreated mesenchymal stem cells mitigate atherosclerosis by regulating the SIRT1/NF‑κB signaling pathway.
The existing evidence for the use of extracellular vesicles in the treatment of osteoporosis: a review.

Front Oncol. 2025 ;15 1532564

Engineered exosomes restore miR-508-5p expression in uterine corpus endometrial carcinoma and reduce tumor progression and metastasis by targeting DLL3.

Yue-Ying Li, Hui Liu, Jia-Lu Feng, Wen-Yan Tian, Juan Du, Li-Ping Zhang.

   Introduction: Endometrial cancer (EC) is a growing global health concern. Understanding the molecular mechanisms driving EC is crucial for developing effective diagnostic and therapeutic strategies. This study investigates the roles of DLL3 and miR-508-5p in EC progression and explores a therapeutic approach using engineered exosomes to modulate their expression.
Methods: TCGA data were analyzed, in vitro and in vivo experiments were performed to assess DLL3 and miR-508-5p function, and bioinformatics was used to confirm their interaction. Mesenchymal stem cells (MSCs) were engineered to produce miR-508-5p-overexpressing exosomes, and their therapeutic effects were tested in mouse models.
Results: Elevated DLL3 and downregulated miR-508-5p were observed in EC and correlated with poor outcomes. miR-508-5p directly targets DLL3. Engineered exosomes restored miR-508-5p, inhibited DLL3, and reduced tumor growth and metastasis in mouse models.
Discussion: The findings highlight the roles of DLL3 and miR-508-5p in EC. Targeting the miR-508-5p/DLL3 axis via exosome-mediated delivery represents a promising therapeutic strategy for EC.

Keywords:  DLL3; endometrial cancer; exosomes; miRNA; tumor progression

DOI:  https://doi.org/10.3389/fonc.2025.1532564
Immunobiology. 2025 Mar 06. pii: S0171-2985(25)00019-1. [Epub ahead of print]230(3): 152885

Harnessing miR-16-5p-Loaded Exosomes from Adipose-Derived Stem Cells to Restore Immune Homeostasis in SLE Patients.

Yin-Hong Zhang, Juan Chen, Wen-Fei Mao, Li-Xi Yan, Fei Long, Sheng-Hao Li, Rui-Xian Zhang.

   BACKGROUND: Systemic Lupus Erythematosus (SLE) is an autoimmune disorder marked by an imbalance between pro-inflammatory Th17 cells and regulatory T cells (Tregs), which contributes to chronic inflammation and multi-organ damage, necessitating novel therapeutic strategies.
METHODS: This study investigates the potential of adipose-derived stem cell (ADSC) exosomes to modulate the Th17/Treg balance in SLE patients through the miR-16-5p/LATS1 axis. Flow cytometry, ELISA, and quantitative real-time PCR were utilized to assess immune cell populations and cytokine levels in SLE patients. Additionally, ADSC exosomes were isolated and characterized, and their impact on CD4+ T cells was evaluated using dual-luciferase and Western blot assays.
RESULTS: SLE patients exhibited increased Th17 cells and decreased Tregs, with corresponding changes in cytokine levels. Reduced miR-16-5p expression was noted in CD4+ T cells, correlating positively with Treg proportions. ADSC-derived exosomes were shown to deliver miR-16-5p effectively, targeting and downregulating LATS1 expression. This modulation restored the Th17/Treg balance and adjusted cytokine expression, indicating an immune regulatory effect.
CONCLUSION: ADSC-derived exosomes, through the miR-16-5p/LATS1 axis, offer a promising therapeutic approach for SLE by restoring immune equilibrium. This study highlights the potential of exosome-based therapies in modulating immune responses, providing a foundation for developing innovative treatments for autoimmune diseases.

Keywords:  ADSC-exos; LATS1; SLE; Th17/Treg; miR-16-5p

DOI:  https://doi.org/10.1016/j.imbio.2025.152885
J Transl Med. 2025 Mar 10. 23(1): 304

Engineered extracellular vesicles promote the repair of acute kidney injury by modulating regulatory T cells and the immune microenvironment.

Lulu Xie, Kaiyue Zhang, Kai Pan, Xiaomin Su, Xiaotong Zhao, Rui Li, Yixin Wang, Haotian Pang, Enze Fu, Zongjin Li.

   BACKGROUND: Acute kidney injury (AKI) is a common and severe clinical condition. However, the underlying mechanisms of AKI have not been fully elucidated, and effective treatment options remain limited. Studies have shown that immune cells play a critical role in AKI, with regulatory T cells (Tregs) being one of the most important immunosuppressive lymphocytes. Tregs proliferation can attenuate AKI, whereas depletion exacerbates kidney injury. Given that endothelial cells (ECs) are the initial cells that interact with immune cells when they invade the tissue parenchyma, ECs are closely associated with immune reactions.
METHODS AND RESULTS: In this study, P-selectin binding peptide-extracellular vesicles (PBP-EVs) that target and repair ECs are engineered. Transcriptome sequencing reveals that PBP-EVs reduce the expression of inflammatory genes in AKI mice. Using high-resolution intravital two-photon microscopy (TPM), an increased recruitment of Tregs in the kidneys of AKI Foxp3-EGFP transgenic mice following PBP-EVs treatment is observed, as well as significant Lgr5+ renal stem cell proliferation in AKI Lgr5-CreERT2; R26mTmG mice. Additionally, PBP-EVs treatment result in reduced infiltration of inflammatory cells, pathological damage and fibrosis of AKI mice. Upon depletion of Tregs in Foxp3-DTR transgenic mice, we observe diminished therapeutic effect of PBP-EVs on AKI.
CONCLUSIONS: The experimental results indicate that PBP-EVs can promote the repair and regeneration of AKI by mitigating endothelial cell damage and subsequently modulating Tregs and the immune microenvironment. These findings provide novel insights and strategies for the treatment of AKI.

Keywords:  Acute kidney injury (AKI); Endothelial cells (ECs); Engineered EVs; Immune microenvironment; Tregs

DOI:  https://doi.org/10.1186/s12967-025-06268-x
Biomed Pharmacother. 2025 Mar 07. pii: S0753-3322(25)00153-2. [Epub ahead of print]185 117959

Exploring the role of exosomes in diabetic neuropathy: From molecular mechanisms to therapeutic potential.

Zohreh Tajabadi, Parisa Alsadat Dadkhah, Mohammad Sadra Gholami Chahkand, Fatemeh Esmaeilpour Moallem, Mohammad Amin Karimi, Ehsan Amini-Salehi, Mehdi Karimi.

  Diabetic neuropathy (DN) is a debilitating complication of diabetes mellitus (DM), characterized by progressive neuronal damage, sensory dysfunction, and impaired quality of life. Recent advances in exosome research have elucidated their crucial role in DN's pathogenesis, diagnosis, and treatment. Exosomes-nanoscale extracellular vesicles-function as vehicles for molecular cargo, including microRNAs (miRNAs), proteins, and lipids, which mediate intercellular communication and regulate key biological processes. Pathologically, hyperglycemia and hyperlipidemia induce the release of exosomes enriched with pathogenic miRNAs, such as miR-130a and miR-20b-3p, which disrupt neuronal function, axonal regeneration, and inflammatory pathways. Conversely, diagnostic studies highlight the utility of exosomal biomarkers like miR-7 and miR-221 in the early detection and monitoring of DN. Therapeutically, Schwann cell-derived and mesenchymal stromal cell (MSC)-derived exosomes demonstrate neuroprotective and reparative effects by enhancing mitochondrial function, modulating inflammation, and promoting axonal repair. Emerging approaches, including engineered exosomes and miRNA-enriched vesicles, further expand their therapeutic potential. Despite these advances, challenges such as standardization, large-scale production, and clinical validation remain in translating these findings into clinical practice. This review underscores the multifaceted roles of exosomes in DN and highlights their potential as innovative tools for precision diagnostics and targeted therapies, paving the way for future research and clinical applications.

Keywords:  Biomarkers; Diabetes; Diabetic neuropathy; Diagnosis; Exosomes; Neuroinflammation; Therapy

DOI:  https://doi.org/10.1016/j.biopha.2025.117959
Mol Med Rep. 2025 May;pii: 126. [Epub ahead of print]31(5):

Exosomes derived from baicalin‑pretreated mesenchymal stem cells mitigate atherosclerosis by regulating the SIRT1/NF‑κB signaling pathway.

Xiaochun Yang, Wei Wu, Weitian Huang, Junfeng Fang, Yunli Chen, Xiaoyan Chen, Xiaolan Lin, Yanbin He.

  Atherosclerosis (AS) is a disease with high global incidence and mortality rates. Currently, the treatment of AS in clinical practice carries a high risk of adverse effects and toxic side effects. The pretreatment of mesenchymal stem cells (MSCs) with drugs may enhance the bioactivity of MSC‑derived exosomes (MSC‑exos), which could be a promising candidate for inhibiting the progression of AS. The aim of the present study was to investigate the ability of exos derived from baicalin‑preconditioned MSCs (Ba‑exos) to exhibit an inhibitory effect on AS progression and to explore the potential molecular mechanisms. Exos were isolated from untreated MSCs and MSCs pretreated with Ba, and were characterized using transmission electron microscopy, nanoparticle tracking analysis and western blotting. Subsequently, Cell Counting Kit‑8 and Transwell assays, reverse transcription‑quantitative PCR, immunofluorescence, western blotting and ELISA were used to evaluate the effects of Ba‑exos on AS, and the possible molecular mechanisms. Oil Red O and Masson staining were used to assess AS pathological tissue in a high‑fat diet‑induced mouse model of AS. Notably, MSC‑exos and Ba‑exos were successfully isolated. Compared with MSC‑exos, Ba‑exos demonstrated superior inhibitory effects on the viability and migration, and the levels of inflammatory factors in oxidized low‑density lipoprotein (ox‑LDL)‑induced vascular smooth muscle cells (VSMCs). Additionally, compared with MSC‑exos, Ba‑exos significantly inhibited NF‑κB activation by upregulating sirtuin 1 (SIRT1), thereby suppressing inflammation in ox‑LDL‑induced VSMCs to a greater extent. In mice with high‑fat diet‑induced AS, Ba‑exos exhibited the ability to inhibit AS plaque formation and to alleviate AS progression by reducing the levels of inflammatory factors compared with MSC‑exos; however, the difference was not significant. In conclusion, Ba‑exos may serve as a potential strategy for treating AS by regulating the SIRT1/NF‑κB signaling pathway to suppress inflammation.

Keywords:  atherosclerosis; baicalin; exosomes; inflammation; mesenchymal stem cells

DOI:  https://doi.org/10.3892/mmr.2025.13491
Int J Surg. 2025 Mar 14.

The existing evidence for the use of extracellular vesicles in the treatment of osteoporosis: a review.

Zixiang Geng, Tiancheng Sun, Long Yuan, Yongfang Zhao.

Osteoporosis is a systemic metabolic bone disease characterized by decreased bone mass, microstructural deterioration, and increased fracture risk. The crucial role of extracellular vesicles(EVs) in the occurrence and development of osteoporosis has garnered attention, with vesicle-based treatments showing significant promise. Compared to conventional osteoporosis medications, EVs possess characteristics of naturalness, selectivity, and adaptability, and more importantly, they have negligible side effects. Hence, this review discusses the applications of natural and engineered extracellular vesicles in osteoporosis are comprehensively outlined. Unfortunately, the absence of consensus on the extraction, purification, characterization, and storage of EVs has resulted in a lack of clinical evidence supporting their application in patients with osteoporosis. Although significant progress is still needed before the clinical use of EVs can be achieved, their substantial potential remains undeniable. Moreover, considering the complexity of bone metabolism in osteoporosis and the heterogeneity of EVs, further investigation into the functional subpopulations of different exosomes will facilitate their application.

DOI: https://doi.org/10.1097/JS9.0000000000002339