bims-engexo 2025-09-21 papers

bims-engexo

Biomed News

on Engineered exosomes

Issue of 2025–09–21
sixteen papers selected by
Ravindran Jaganathan, Universiti Kuala Lumpur

In situ reprogramming of fibroblasts into antigen-presenting pseudo-dendritic cells via IFN-β-engineered protoplast-derived exosomes delivered by microneedle arrays to enhance adaptive immunity.
Exosome-Based Therapeutics for Musculoskeletal Disorders: Advances in Engineering, Targeting, and Biomaterial Integration.
Exosomes as Emerging Therapeutic Platforms in Neurological and Psychiatric Disorders.
Comparison of therapeutic potential of macrophage- or mesenchymal stem cell-derived exosomes in pancreatic cancer: An updated review.
Targeting SIRT1 via Exosomes Derived From Oleuropein-Treated Cells: A Novel Approach to Rejuvenation Skin Through miRNA Modulation.
Exosome from adipose-derived stromal vascular fraction enhances the proliferation of human dental pulp stem cells.
Ox-LDL-stimulated macrophage-derived exosomes regulate adipose tissue remodeling and promote the progression of atherosclerosis.
Molecular regulatory mechanisms and diagnostic potential of dendritic cell-derived exosomes in liver transplantation: from immune tolerance induction to translational challenges.
Unveiling the intricacies of exosome biology: from biogenesis to therapeutic applications.
Exosomal microRNAs in Different Disease Activity Status in Systemic Lupus Erythematosus: A Retrospective Study.
Enhancement of circular RNA 0002577 in serum exosomes in patients with endometrial cancer accelerates disease progression via general transcription factor II-I repeat domain-containing 1 (GTF2IRD1).
The Anti-Aging Effects of Adipose-Derived Mesenchymal Stem Cell Exosomes on Skin and Their Potential for Personalized Skincare Applications.
MiRNA sequencing of platelet and exosome revealed platelet miR-199b-3p as a potential biomarker in lung adenocarcinoma.
Emerging exosomal biomarkers for essential hypertension: a systematic review.
[Exosomes derived from mesenchymal stem cells alleviate white matter damage in neonatal rats by targeting the NLRP3 inflammasome].
Sustained antidepressant actions of ketamine involve TAMM41-mediated transfer of astrocytic sigma-1 receptor to neuron.

Theranostics. 2025 ;15(17): 9179-9199

In situ reprogramming of fibroblasts into antigen-presenting pseudo-dendritic cells via IFN-β-engineered protoplast-derived exosomes delivered by microneedle arrays to enhance adaptive immunity.

Yue Yin, Shijie Zhao, Wei Li, Yuan Cui, Thanh Loc Nguyen, Ge Gao.

  Rationale: Dendritic cells (DCs) play a crucial role in adaptive immune responses; however, ex vivo differentiation strategies face operational complexities and reduced cellular viability. In situ reprogramming of resident cells into antigen-presenting cells represents a promising alternative approach for enhancing local immune responses. Methods: We initially introduce the novel concept of pseudo-DCs, in situ transforming intradermal fibroblasts into DC-like cells using an engineered exosome-loaded microneedle (MN) array. Specifically, engineered nano-protoplasts expressing interferon-beta (IFN-β) and loaded with varicella-zoster virus glycoprotein E (VZV gE) were used to stimulate DCs and derive immunostimulatory exosomes. These exosomes were integrated into a microarray-based delivery system for intradermal application. Results: The engineered exosomes (IdE@E) induced resident fibroblasts to upregulate DC surface co-stimulatory markers (CD80/86) and effectively present the model antigen. Transcriptome analysis also revealed significant upregulation of genes associated with immune response and antigen presentation in IdE@E-treated cells. In vivo studies demonstrated that MN array-delivered IdE@E effectively induced the expression of DC and activation markers from fibroblasts in dermis. Furthermore, MN array-delivered IdE@E significantly elevated the population of IFN-γ+CD8+ T cells in both lymph nodes and spleen, indicating enhanced local and systemic immune responses. Conclusions: This novel in situ reprogramming method represents a paradigm shift in precision immunotherapies, leveraging exosome-mediated cellular mimicry to enhance adaptive immunity without complete cellular transformation. This scalable framework holds significant promise for immunotherapy and could revolutionize personalized immunotherapy.

Keywords:  adaptive immunity; dendritic cell; exosome-loaded microneedle arrays; fibroblast; in situ reprogramming

DOI:  https://doi.org/10.7150/thno.115080
ACS Nano. 2025 Sep 17.

Exosome-Based Therapeutics for Musculoskeletal Disorders: Advances in Engineering, Targeting, and Biomaterial Integration.

Zehui Lv, Jiawei Xu, Xuejie Cai, Yingjie Wang, Xingdong Yang, Han Wang, Yang Zhu, Bin Feng, Xisheng Weng.

  Musculoskeletal disorders represent an escalating global challenge that adversely affects both the quality of life and healthcare systems. Despite the availability of conventional therapeutic approaches, these methods are constrained by inadequate targeting, limited tissue regeneration capabilities, and potential long-term safety concerns. In recent years, exosomes have emerged as promising agents for precise intervention and functional regeneration, owing to their properties of active targeting, cargo delivery capability, modifiability, and biocompatibility, particularly when used in conjunction with engineering and biomaterial delivery strategies. While the therapeutic potential of exosomes in the management of musculoskeletal diseases is increasingly acknowledged, the current literature lacks a comprehensive integration of three critical dimensions: exosome engineering strategies, advanced biomaterial delivery systems, and their prospective therapeutic applications across various diseases. Therefore, this study concentrates on engineering methodologies aimed at augmenting the therapeutic efficacy of exosomes, encompassing the pretreatment of blast cells, the modification of exosomes, and their incorporation with biomaterials. Furthermore, we systematically introduce delivery systems utilizing hydrogels, scaffolds, microneedles, and fiber membranes, which enhance exosome delivery by facilitating spatial positioning control and achieving sustained release effects. Building on this foundation, we conduct an in-depth examination of the mechanisms and applications of exosomes in the treatment of musculoskeletal disorders. Additionally, this review provides the analysis of biogenesis, isolation, extraction, and preservation strategies of exosomes while also identifying the key factors impeding their clinical application. Based on this synthesis, we propose that exosomes represent a transformative paradigm for targeted, minimally invasive, and tissue-specific interventions in musculoskeletal medicine.

Keywords:  biomaterials; cargo loading; delivery systems; exosomes; modified strategies; musculoskeletal disorders; targeted therapy; tissue engineering

DOI:  https://doi.org/10.1021/acsnano.5c05416
Pharmaceut Med. 2025 Sep 19.

Exosomes as Emerging Therapeutic Platforms in Neurological and Psychiatric Disorders.

Ram Mohan Ram Kumar, Logesh Rajan, Saravana Babu Chidambaram.

Exosomes, small extracellular vesicles (sEVs) that range in Size from 30 to 150 nm in diameter, have emerged as crucial mediators of intercellular communication within the central nervous system (CNS). They play significant roles in the pathogenesis and progression of various neurological and psychiatric disorders, including Alzheimer's disease, Parkinson's disease, ischemic stroke, depression, bipolar disorder, and autism spectrum disorder. Exosomes carry a diverse cargo of proteins, nucleic acids, lipids, and other bioactive molecules that can influence neuronal function and synaptic plasticity. In disease states, exosomes derived from stressed neurons or glial cells can propagate neuroinflammation, synaptic dysfunction, and cognitive decline. They may also mediate the spread of abnormal proteins or microRNAs, disrupting neuronal connectivity and neurotransmitter signaling and contributing to the development of proteinopathies and neurotoxicity. Owing to their presence in bodily fluids such as blood plasma, cerebrospinal fluid, and saliva, exosomes hold promise as biomarkers for these disorders. Moreover, their regulatory roles present new opportunities for developing novel diagnostic biomarkers and therapeutic interventions. This review provides an overview of the multifaceted roles of exosomes in neurological and psychiatric disorders. We delve into their contributions to disease pathogenesis, their potential as diagnostic biomarkers, and the innovative therapeutic strategies leveraging exosome-based delivery systems. By exploring the current state of research, we aim to highlight the translational potential of exosomes in revolutionizing the diagnosis and treatment of these disorders.

DOI: https://doi.org/10.1007/s40290-025-00584-9
World J Stem Cells. 2025 Aug 26. 17(8): 107400

Comparison of therapeutic potential of macrophage- or mesenchymal stem cell-derived exosomes in pancreatic cancer: An updated review.

Demet Kacaroglu, Nilgun Gurbuz.

  Pancreatic cancer is known to have high metastatic potential and low survival rates due to the failure of the therapeutic agents to reach the cancer cells having the dense desmoplastic microenvironment. Exosomes are considered to be a promising therapeutic agent carrier due to their advantages such as low immunogenicity and easy targeting. More researches and future developments are needed, although exosome-based therapies need further research and development before they can be translated into clinical applications. In this review, we aimed to discuss comparatively two main exosome sources as mesenchymal stem cell (MSC)-derived and macrophage-derived exosomes on pancreatic cancer in terms of the therapeutic potential, advantages, disadvantages and also other comprehensive details. In vitro, in vivo and clinical phase studies examining the therapeutic potential of MSC-derived and macrophage-derived exosomes in pancreatic cancer will be discussed. We strongly believe that this review will guide the new investigations related to exosome-based targeted therapy in pancreatic cancer. In the meantime, we aimed to provide an overview of ongoing research on MSC and macrophage exosome-based therapies, focusing on their role in cancer treatment, particularly for pancreatic cancer. By examining current findings, this review will provide a broad perspective on the therapeutic potential and limitations of exosomes.

Keywords:  Exosomes; Macrophage exosomes; Mesenchymal stem cell exosomes; Pancreatic cancer; Small extracellular vesicles

DOI:  https://doi.org/10.4252/wjsc.v17.i8.107400
Food Sci Nutr. 2025 Sep;13(9): e70964

Targeting SIRT1 via Exosomes Derived From Oleuropein-Treated Cells: A Novel Approach to Rejuvenation Skin Through miRNA Modulation.

Naeimeh Safavizadeh, Zahra Noormohammadi, Mohammad Zaefizadeh, Kazem Nejati Koshki.

  Sirtuin1 (SIRT1) plays an important role in skin aging by regulating cellular processes such as oxidative stress response, inflammation modulation, Collagen and Elastin synthesis. This study aims to examine oleuropein's (OLE) effect on SIRT1 gene expression and to analyze SIRT1-related miRNAs in exosomes produced from Mesenchymal Stem cells (MSC) and Human Fetal Foreskin Fibroblast 2 (HFFF2) cells, along with these treated exosomes' impact on SIRT1 gene expression and the studied miRNAs in HFFF2 cells to decrease skin aging. A nontoxic concentration (400 μg/mL) of OLE was applied to the MSCs and HFFF2 cells. Then, Gradient Ultracentrifugation extracted their exosomes; cell-derived exosomes were confirmed by DLS assay and western Blot. Exosomes were applied at 50 μg/mL (exosome protein concentration) to HFFF2 cells. The expression of SIRT1 gene and related miRNAs relative to the control group were examined using qRT-PCR. This analysis was conducted on cells OLE-treated for SIRT1, on exosomes treatment with OLE for miRNAs, and on HFFF2 cells treated with cell-derived exosomes for both SIRT1 and miRNAs. SIRT1 expression was upregulated (p ≤ 0.05) in both OLE and cell-derived exosomes. Also, hsa-miR-29c-3p and hsa-miR-9-5p were downregulated (p ≤ 0.05), whereas hsa-miR-155-5p was upregulated (p ≤ 0.05) in exosomes OLE-treated and in HFFF2 cells treated with these exosomes. This study introduces a novel approach to skin rejuvenation by using manipulated exosomes OLE-treated, which enhance SIRT1 expression and suppress related miRNAs. This method potentially offers a more effective and less immunogenic alternative to direct OLE application due to the exosomes' ability to penetrate cells.

Keywords:  SIRT1; exosome; miRNAs; oleuropein

DOI:  https://doi.org/10.1002/fsn3.70964
J Conserv Dent Endod. 2025 Sep;28(9): 886-891

Exosome from adipose-derived stromal vascular fraction enhances the proliferation of human dental pulp stem cells.

Sylva Dinie Alinda, Anggraini Margono, Indah Julianto, Dini Asrianti Bagio.

   Objectives: In regenerative dentistry, cell proliferation is crucial for tissue repair and immune response modulation, essential for successful regeneration. The adipose-derived stromal vascular fraction (AD-SVF) shows promise in tissue engineering as an autologous therapy. AD-SVF exosomes, cell-free and resilient in ischemic conditions, offer an ethical and hopeful strategy for dental tissue regeneration and wider regenerative medicine use. Although the enhancement of human dental pulp stem cells (hDPSCs) migratory abilities by AD-SVF exosomes is known, their impact on hDPSC proliferation requires further examination.
Aims: This study explores how AD-SVF exosomes influence hDPSC proliferation.
Methods: AD-SVF exosomes, isolated using size exclusion chromatography and characterized through flow cytometry and nanoparticle tracking analysis, were used to treat hDPSCs at varying concentrations. Proliferation was assessed with the cell counting kit-8 assay. Statistical analysis involved one-way ANOVA, post hoc LSD testing, with significance at 0.05.
Results and Conclusion: Isolated AD-SVF exosomes, averaging 103 ± 24 nm, expressed CD9+ and CD63+ markers. The study revealed increased hDPSC proliferation on the 5th day post low-exosome treatment, indicating a positive association between AD-SVF exosomes and cell proliferation. These results highlight the potential of AD-SVF exosomes to enhance hDPSC proliferation for dental pulp and broader tissue regeneration.

Keywords:  Adipose-derived stromal vascular fraction; dental pulp stromal cells; exosomes; proliferation; regenerative endodontics

DOI:  https://doi.org/10.4103/JCDE.JCDE_427_25
Mol Cell Endocrinol. 2025 Sep 16. pii: S0303-7207(25)00211-4. [Epub ahead of print] 112660

Ox-LDL-stimulated macrophage-derived exosomes regulate adipose tissue remodeling and promote the progression of atherosclerosis.

Xiaoyu Liu, Guoyan Xu, Yunlu Xu, Yuling Xu.

   BACKGROUND: Atherosclerosis (AS) is a chronic vascular disease, and perivascular adipose tissue dysfunction is an important cause of the arterial plaque formation involved. However, the underlying mechanism has not been fully elucidated. The aim of this study was to investigate the mechanism of oxidized low-density lipoprotein (ox-LDL) stimulation of macrophage-derived exosomes in the development of AS.
METHODS: We isolated exosomes from ox-LDL-treated macrophages and injected them into Western diet-fed ApoE-/- mice. We assessed AS, lipid metabolism, and endothelial function by histology, ELISA, qPCR, and western blotting, and examined BMP7 and OPA1 regulation in brown fat and vascular endothelium.
RESULTS: Macrophage-derived exosomes were extracted, and their size was determined by transmission electron microscopy. Additionally, CD9, CD63, and TSG101 protein expression within these macrophages was determined. Compared with the control group, the exosomes group showed increased expression of AP2 and PPAR and decreased expression of UCP-1, PGC-1α, and BMP7. Furthermore, when BMP7 was knocked down, the expression of the lipid metabolites FASN, SCD1, HSL, and ATGL as well as of OPA1 decreased. In an ApoE-/- mouse model, compared to the control group, increased arterial plaques and plaque lesion formation were observed in the exosome group, along with elevated expression of the lipid metrics TC, TG, LDL-C, and HDL-C and significant increases in the expression of the proinflammatory factors VCAM1, ICAM1, MCP-1, and IL-6. Consequently the progression of AS was aggravated in this group.
CONCLUSIONS: This study demonstrated that ox-LDL stimulated exosome secretion from macrophages, accelerating the AS process. It also showed that, mechanistically, BMP7 regulates the expression of OPA1 and affects the normal lipid metabolism, thereby accelerating AS.

Keywords:  BMP7; OPA1; atherosclerosis; exosomes; perivascular adipose tissue

DOI:  https://doi.org/10.1016/j.mce.2025.112660
Front Immunol. 2025 ;16 1657956

Molecular regulatory mechanisms and diagnostic potential of dendritic cell-derived exosomes in liver transplantation: from immune tolerance induction to translational challenges.

Xiaopeng Chen, Zhiqi Yang, Minghao Li.

  Liver transplantation remains the only curative treatment for end-stage liver disease (ESLD); however, immune rejection significantly hampers its long-term success. Dendritic cell-derived exosomes (DEXs) have emerged as a promising tool for inducing immune tolerance and enabling precise immunomodulation in liver transplantation, owing to their unique bidirectional immunoregulatory capabilities. This review systematically summarizes the biological characteristics and functional properties of DEXs, with a particular focus on their multidimensional regulatory mechanisms within the hepatic transplant immune microenvironment. These include: the mechanisms and pathways by which DEXs mediate immune tolerance; the synergistic immunoregulatory roles of DEXs and exosomes derived from other immune cells. Furthermore, we explore the potential of DEXs for integrated diagnostic and therapeutic applications, engineering upgrades to treatment strategies, and their prospects for clinical translation. Despite their promise, several challenges persist, including difficulties in exosome isolation and purification, prolonged preparation times, bioengineering limitations, and the lack of effective in vivo tracking methods. We propose that advancements in artificial intelligence, biomaterials science, and interdisciplinary technologies may help overcome these barriers, facilitating the precise isolation, functional optimization, and clinical translation of DEXs. This review emphasizes the molecular immunoregulatory networks governed by DEXs and discusses their translational pathways, aiming to promote individualized diagnostic and therapeutic strategies in liver transplantation.

Keywords:  clinical translation; dendritic cells; exosomes; immune tolerance; liver transplantation

DOI:  https://doi.org/10.3389/fimmu.2025.1657956
Histochem Cell Biol. 2025 Sep 17. 163(1): 92

Unveiling the intricacies of exosome biology: from biogenesis to therapeutic applications.

Angel Mendonca, Aparajita Acharjee, Yash Sansare, Sujatha Sundaresan.

  Exosomes are small membrane-bound nanovesicles that are secreted by cells when multivesicular bodies merge with the plasma membrane. These particles have been demonstrated to carry specific proteins, lipids and genetic components that are exclusive to each cell type. These compounds can be selectively taken up by cells in close proximity or at a distance, even after being released, thus altering their biological response. Therefore, the regulated manufacturing of exosomes, the exact makeup of their contents and their capacity to selectively interact with particular cells are highly important in the field of biology because of the immense potential of exosomes as noninvasive diagnostic biomarkers and therapeutic nanocarriers. This review presents a comprehensive examination and evaluation of the most recent progress in comprehending the regulatory mechanisms of exosome formation, the molecular composition of exosomes and the approaches utilised in exosome research. Furthermore, this review focuses on the potential use of exosomes as promising markers for the diagnosis and prognosis of medical conditions, owing to their specific associations with cellular lineage and state. In addition, the potential role of exosomes as vehicles for the delivery of medicines and genes for therapeutic applications is unraveled. The study of exosomes is currently in a nascent phase. Acquiring a thorough understanding of the subcellular constituents and processes implicated in exosome generation, together with their specific cell targeting, can yield valuable insights into their physiological roles.

Keywords:  Biogenesis; Biomarkers; Characterisation; Exosomes; Theranostics

DOI:  https://doi.org/10.1007/s00418-025-02418-w
Arch Rheumatol. 2025 Sep 01. 40(3): 323-331

Exosomal microRNAs in Different Disease Activity Status in Systemic Lupus Erythematosus: A Retrospective Study.

Wenyu Xu, Peiying Nie, Qian Li, Bingjie Gu, Qijie Ren, Xingguo Chen.

Background/Aims: Differential miRNA expression profiles in the plasma exosomes of systemic lupus erythematosus (SLE) patients were obtained at various disease activity stages and compared with healthy controls. Materials and Methods: Plasma samples were collected from 48 SLE patients with high, medium, and low disease activity and from 20 healthy controls. The sample set was retrospectively analyzed for differences in clinical features. Plasma exosomes were extracted and subjected to comprehensive detection and analysis. Total exosomal RNA was extracted from the 4 groups, and differential expression profiles were analyzed using miRNA chip technology. Results: Significant differences in clinical parameters-including platelet count (PLT), erythrocyte sedimentation rate (ESR), 24-hour urinary protein, and complement C3/C4 levels-were observed among SLE patients with different disease activity levels (all P < .05). Plasma exosomes were successfully isolated and characterized. Microarray analysis identified distinct exosomal miRNA profiles. Notably, let-7a-5p and miR-23a-3p were significantly downregulated in patients with high disease activity compared to those with low activity (fold change > 2, P < .0001), while miR-4532 was markedly upregulated. Correlation analysis showed let-7a-5p expression was positively associated with PLT (r = 0.61) and complement C3 (r = 0.69) and negatively with ESR (r = -0.65). Conversely, miR-4532 was positively correlated with ESR (r = 0.67) and urinary protein (r = 0.56) and negatively with C3 and C4 (both r = -0.67). Conclusion: Differential miRNA expression was identified in the exosomes of SLE patients at various disease activity levels. These findings indicate the crucial role of these miRNAs in the onset and progression of SLE, providing a basis for further investigation of the immunoregulatory functions of exosomes.

DOI: https://doi.org/10.5152/ArchRheumatol.2025.11027
J Gynecol Oncol. 2025 Sep 10.

Enhancement of circular RNA 0002577 in serum exosomes in patients with endometrial cancer accelerates disease progression via general transcription factor II-I repeat domain-containing 1 (GTF2IRD1).

Yueying Li, Ya Liu, Jialu Feng, Juan Du, Wenyan Tian, Liping Zhang.

   OBJECTIVE: Uterine corpus endometrial carcinoma (UCEC) is a common gynecologic malignancy with poor prognosis in advanced stages. Circular RNA (circRNA) and exosomes have been documented as significant contributors to the advancement of tumor cells, but the specific regulatory mechanisms between them is unclear. Therefore, our study attempts to explore the mechanism between them.
METHODS: Firstly, we isolated and identified exosomes, and then validated their role in UCEC progression by experiments in vivo and in vitro. Secondly, a human competing endogenous RNA (ceRNA) array was used to identify the circRNA with the most significant differences in expression from serum of UCEC patient, and validated its role in UCEC progression by experiments in vitro. Then, we find the target gene of this circRNA by RNA sequencing, and further clarify the correlation between the 2 and their role in tumor cell progression through experiments in vitro.
RESULTS: Serum exosomes in patients with UCEC can promote the progression of UCEC. The human ceRNA array identified that circRNA 0002577 (circ_0002577) was up-regulated and was the most significantly altered circRNA. Moreover, the up-regulated circ_0002577 in exosomes derived from UCEC patients promote proliferation and migration of UCEC. Based on RNA sequencing results, general transcription factor II-I repeat domain-containing 1 (GTF2IRD1) gene was identified as being highly correlated with circ_0002577. Additionally, a positive correlation between circ_0002577 and GTF2IRD1 was confirmed by experiments in vitro.
CONCLUSION: Exosomes promote UCEC progression through circ_0002577 mediated regulation of GTF2IRD1, highlighting the potential therapeutic targets in treatment for UCEC.

Keywords:  Endometrial Neoplasms; Exosomes; RNA, Circular

DOI:  https://doi.org/10.3802/jgo.2026.37.e17
Clin Cosmet Investig Dermatol. 2025 ;18 2267-2284

The Anti-Aging Effects of Adipose-Derived Mesenchymal Stem Cell Exosomes on Skin and Their Potential for Personalized Skincare Applications.

Yan-Xiu Jin, Guang-Zhen Jin.

  Stem cell-derive exosomes have gained increasing attention in the skincare industry in recent years due to their multiple anti-aging benefits. However, differences in cell sources lead to significant heterogeneity in the composition of secreted exosomes, resulting in inconsistent biological effects. Moreover, the lack of standardized production protocols and the technical challenges associated with large-scale manufacturing continue to limit their broader application in the beauty industry. As a narrative review, this article systematically summarizes the biological functions and mechanisms of action of autologous adipose mesenchymal stem cell-derived exosomes (AMSCs-Exos) in anti-skin aging, covering in vitro, in vivo, and clinical studies. Recent studies have shown that autologous exosomes derived from AMSCs not only possess the common bioactivity shared by stem cell-derived exosomes but also exhibit higher biocompatibility and a lower risk of pathogen transmission. In addition, their suitability for small-scale production makes them a more advantageous option. Furthermore, advances in artificial intelligence (AI) technology are driving the transformation of the cosmetics industry from traditional skincare to personalized skincare: AI provides a basis for the personalized matching of exosome dosage and delivery methods through high-precision skin condition monitoring. It optimizes the iteration of customized exosome products by integrating intelligent analysis of dynamic changes in users' skin texture and usage feedback, and achieves closed-loop management from "universal formulations" to "precision repair" by combining skin physiological data with user preferences. The integration of AI with AMSCs-Exos not only expands their potential in personalized skincare applications but also holds promise for generating valuable clinical data, thereby further advancing the concept and scientific development of precision skincare.

Keywords:  adipose-derived mesenchymal stem cells; anti-skin aging; artificial intelligence; customized cosmetics; exosomes; personalized skincare

DOI:  https://doi.org/10.2147/CCID.S547675
Front Immunol. 2025 ;16 1619448

MiRNA sequencing of platelet and exosome revealed platelet miR-199b-3p as a potential biomarker in lung adenocarcinoma.

Xiaoxia Wen, Sisi Yu, Ping Leng, Yu Liu, Huaichao Luo.

   Background: Distinguishing malignant lung adenocarcinoma (LAC) from benign pulmonary nodules (BPN) is a major clinical challenge. While exosomal microRNAs (miRNAs) are established liquid biopsy biomarkers, tumor-educated platelet miRNAs represent an emerging source. However, a direct comparison of the diagnostic potential between these two sources, and the identification of reliable platelet miRNA biomarkers for LAC, remain poorly defined. Critically, the well-documented interaction between tumor-derived exosomes and platelets, which complicates exosome isolation due to inevitable platelet contamination, raises a pivotal question: Could the analysis of platelet miRNA, a far easier-to-isolate component, offer a viable and efficient alternative to exosome-based diagnostics?
Methods: We performed miRNA sequencing (miRNA-seq) on paired peripheral blood platelets and plasma exosomes from healthy donors (HD), BPN, and LAC patients. The abundance and diversity of miRNAs were compared. Candidate reference miRNAs for platelet studies were screened and validated using RT-qPCR and multiple stability algorithms. Differentially expressed platelet miRNAs were identified and validated in a cohort of 133 subjects (70 LAC, 31 HD, 32 BPN). The diagnostic performance of the top candidate was evaluated using ROC analysis and Net Reclassification Index (NRI) against traditional biomarkers (CEA) and clinical models. Target genes were predicted using bioinformatic tools and validated with public databases (TCGA, UALCAN, GEPIA).
Results: Platelets contained significantly greater miRNA diversity and abundance compared to exosomes. Differentially expressed platelet miRNAs showed higher concordance with tissue-specific signatures than their exosomal counterparts. hsa-let-7i-5p was identified as the most stable reference miRNA for normalizing platelet miRNA expression in LAC. hsa-miR-199b-3p was significantly downregulated in the platelets of LAC patients compared to both HD and, crucially, BPN patients. It effectively distinguished LAC from BPN (AUC = 0.73) and early-stage LAC (Stage I) from BPN (AUC = 0.72), outperforming traditional biomarkers (CEA) and clinical models, as confirmed by significant NRI values. The diagnostic value of miR-199b-3p was also significant in the non-GGN subgroup (p=0.037). Bioinformatic analysis predicted KTN1 as a key target gene, with an inverse correlation to miR-199b-3p in LAC tissues and association with poor prognosis. Intriguingly, KTN1 expression in platelets was also dysregulated, suggesting a complex platelet-tumor interaction.
Conclusion: This study demonstrates that platelet miRNAs are a superior source for liquid biopsy in LAC compared to exosomal miRNAs. We establish hsa-let-7i-5p as a reliable reference gene and identify platelet hsa-miR-199b-3p as a promising non-invasive biomarker for the differential diagnosis of malignant and benign pulmonary nodules, offering a new avenue for the early detection of lung adenocarcinoma.

Keywords:  exosome; hsa-miR-199b-3p; liquid biopsy; lung adenocarcinoma; miRNA sequencing; platelet; reference miRNA

DOI:  https://doi.org/10.3389/fimmu.2025.1619448
Cardiovasc Diagn Ther. 2025 Aug 30. 15(4): 915-926

Emerging exosomal biomarkers for essential hypertension: a systematic review.

Dongling Zhong, Yuan Chen, Yue Zhang, Qian Liang, Chen Xue, Jiayi Chen, Rongjiang Jin, Juan Li, Xiaolin Yang.

   Background: Exosomes show promise as biomarkers for essential hypertension (EH) progression and complications. However, existing studies on dysregulation of exosomal biomarkers in hypertension lack consistency. Thus, we conducted a comprehensive systematic review to synthesize evidence on exosomal biomarkers associated with EH.
Methods: We performed an exhaustive search across PubMed, Embase, Web of Science, the Cochrane Library, China National Knowledge Infrastructure, Wanfang Database, and Chinese Clinical Trial Registry. Our search encompassed all available Chinese and English records from their inception through August 14th, 2025, without any restrictions on study design. The primary outcome focused on exosomal microRNA (miRNA) alterations, with secondary analyses of other cargo types (e.g., proteins). We employed the Joanna Briggs Institute (JBI) critical appraisal tool and the risk of bias in non-randomized studies of interventions (ROBINS-I) tool to assess the risk of bias. Due to the limitations of the data in the included studies, we conducted a qualitative narrative synthesis to summarize key study characteristics and synthesize their principal findings. The protocol was prospectively registered on PROSPERO (CRD42023470885).
Results: The qualitative analysis included 11 identified studies, which revealed moderate-to-high methodological quality (JBI: 6 moderate, 4 high), with one study exhibiting a moderate risk of bias (ROBINS-I). This systematic review revealed that exosomal biomarkers in blood and urine had diagnostic potential for hypertension and its complications. Evidence suggested that exosomal biomarkers were associated with hypertensive vascular dysfunction (e.g., increased miR-320d/423-5p) and may provide a molecular basis for precise typing of hypertension (platelet-derived extracellular vesicles). Notably, exosomal biomarkers may serve as indicators of target organ damage, reflecting early renal injury (decreased miR-26a-5p) and cognitive dysfunction (decreased miR-330-3p) in hypertension.
Conclusions: This systematic review highlights the value of blood and urine exosomal biomarkers in the early diagnosis, precise typing, and monitoring of target organ damage in hypertension and its complications. Future studies should systematically compare exosomal biomarkers with conventional markers using standardized protocols. Methodological improvements should focus on expanding larger sample sizes, enhancing reporting completeness and transparency, and standardizing data-sharing practices.

Keywords:  Exosome; essential hypertension (EH); exosomal microRNA (exosomal miRNA); exosomal protein; systematic review

DOI:  https://doi.org/10.21037/cdt-2025-76
Zhongguo Dang Dai Er Ke Za Zhi. 2025 Sept 15;27(9):pii: 1008-8830(2025)09-1119-09. [Epub ahead of print]27(9): 1119-1127

[Exosomes derived from mesenchymal stem cells alleviate white matter damage in neonatal rats by targeting the NLRP3 inflammasome].

Chao Wang, Yan-Ping Zhu, Bayiercaicike, Yu-Qing Feng, Yan-Mei Wang.

   OBJECTIVES: To investigate whether mesenchymal stem cell-derived exosomes (MSC-Exo) alleviate white matter damage (WMD) in neonatal rats by targeting the nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3).
METHODS: Three-day-old Sprague-Dawley rats were randomly assigned to four groups: Sham, hypoxia-ischemia (HI), MSC-Exo, and MCC950 (NLRP3 inhibitor) (n=24 per group). The WMD model was established by unilateral common carotid artery ligation combined with hypoxia. Exosomes (1×108 particles/μL) were transplanted into the lateral ventricle using stereotaxic guidance. Fourteen days after modeling, hematoxylin-eosin staining was used to observe pathological changes in brain tissue, and transmission electron microscopy was used to assess myelinated axons. Western blotting was performed to detect the expression of myelin basic protein (MBP), NLRP3, caspase-1, and interleukin-1β (IL-1β). Immunohistochemistry was used to measure NLRP3, caspase-1, and IL-1β expression. Twenty-eight days post-modeling, behavioral changes were evaluated using the Morris water maze.
RESULTS: In the HI group, marked inflammatory cell infiltration, extensive vacuolation, and decreased numbers of myelinated axons were observed compared to the Sham group. The MSC-Exo group showed reduced inflammatory infiltration, fewer vacuoles, and increased myelinated axons compared to the HI group, while the MCC950 group showed nearly normal cell morphology. Compared to the Sham group, the HI group exhibited decreased MBP expression, fewer platform crossings, shorter time in the target quadrant, increased expression of NLRP3, caspase-1, and IL-1β, and longer escape latency (all P<0.05). Compared to the HI group, the MSC-Exo and MCC950 groups showed increased MBP expression, more platform crossings, longer target quadrant stay, and reduced NLRP3, caspase-1, and IL-1β expression, as well as shorter escape latency (all P<0.05).
CONCLUSIONS: MSC-Exo may attenuate white matter damage in neonatal rats by targeting the NLRP3 inflammasome and promoting oligodendrocyte maturation.

Keywords:  Exosome; Mesenchymal stem cell; Neonatal rat; Nucleotide-binding oligomerization domain-like receptor protein 3; White matter damage

DOI:  https://doi.org/10.7499/j.issn.1008-8830.2504160
Mol Psychiatry. 2025 Sep 16.

Sustained antidepressant actions of ketamine involve TAMM41-mediated transfer of astrocytic sigma-1 receptor to neuron.

Lin Guo, Xinting Lin, Qinghua Wang, Ziyu Liu, Siyu Liu, Na Lv, Zhidong Liu, Yinan Wang, Congcong Sun, Yun Wang.

Several limitations such as delayed onset and insufficient efficacy exist in current antidepressant treatments, thereby driving the search for new therapeutic approaches. Ketamine produces a rapid and sustained antidepressant response, yet its molecular mechanisms remain elusive. Here, we elucidated that the transfer of sigma-1 receptor (S1R) from astrocytes to neurons was associated with ketamine's antidepressant effect. Mechanistically, we identified that ketamine activated the mitochondrial protein TAMM41 and then facilitated the transfer of astrocytic S1R via the TAMM41-cardiolipin-exosomes axis. Furthermore, conditional deletion of astrocytic TAMM41 exhibited depressive-like behaviors and abolished the sustained antidepressant effect of ketamine. Inspired by these findings of endogenous exosomes delivering S1R, we devised a strategy to engineer exosome-encapsulated S1R (S1R-EXOs) using exosomes released by human red blood cells and synthetic S1R mRNA. We found that exogenous S1R-EXOs effectively delivered S1R to neurons in S1R knockout mice. Finally, we verified that exogenous S1R-EXOs produced antidepressant-like effect. Our findings reveal that astrocytic TAMM41 underlies the sustained antidepressant effect of ketamine through exosomal delivery of S1R to neurons, offering potential for new strategies in depression treatment. Considering the advantages of human red blood cells and therapeutic mRNA, our results also provide a promising avenue that warrants further translational and clinical exploration.

DOI: https://doi.org/10.1038/s41380-025-03248-x