bims-engexo Biomed News
on Engineered exosomes
Issue of 2025–04–27
nine papers selected by
Ravindran Jaganathan, Universiti Kuala Lumpur
  1. Cutting-Edge Progress in the Acquisition, Modification and Therapeutic Applications of Exosomes for Drug Delivery.
  2. Role of Toll-like receptors in exosome biogenesis and angiogenesis capacity.
  3. Therapeutic Potential of Exosomal miRNAs: New Insights and Future Directions.
  4. Effects of low-intensity pulsed focal ultrasound-mediated delivery of endothelial progenitor-derived exosomes in tMCAo stroke.
  5. Exploring the mechanism of bone marrow mesenchymal stromal cell exosomes in respiratory syncytial virus infection based on miRNA sequencing.
  6. Exosomes as key mediators in immune and cancer cell interactions: insights in melanoma progression and therapy.
  7. Evaluating purified exosome product and its role in neurologic and functional recovery following spinal cord injury in female rats.
  8. Effects of 3D-printed exosome-functionalized brain acellular matrix hydrogel on neuroinflammation in rats following cerebral hemorrhage.
  9. Exosomes secreted from adipose-derived stem cells inhibit M1 macrophage polarization ameliorate chronic endometritis by regulating SIRT2/NLRP3.
  1. Int J Nanomedicine. 2025 ;20 5059-5080
    Cutting-Edge Progress in the Acquisition, Modification and Therapeutic Applications of Exosomes for Drug Delivery.
    Yuhao Wang, Shengmeng Yuan, Lihua Zhou, Kexin Yang, Zhaorui Jin, An Lin, Chao Yang, Weidong Tian.
      Exosomes are vesicles secreted by cells, typically ranging from 30 to 150 nm in diameter, and serve as crucial mediators of intercellular communication. Exosomes are capable of loading various therapeutic substances, such as small molecule compounds, proteins, and oligonucleotides, thereby making them an ideal vehicle for drug delivery. The distinctive biocompatibility, high stability, and targeting properties of exosomes render them highly valuable for future treatments of diseases like cancer and cardiovascular diseases. Despite the potential advantage of exosomes in delivering biologically active molecules, the techniques for the preparation, purification, preservation, and other aspects of stem cell exosomes are not yet mature enough. In this paper, we briefly introduce the composition, biogenesis, and benefits of exosomes, and primarily focus on summarizing the isolation and purification methods of exosomes, the preparation of engineered exosomes, and their clinical applications, to better provide new ideas for the development of exosome drug delivery systems.
    Keywords:  applications; drug delivery; engineered exosomes; exosomes; isolation; preservation
    DOI:  https://doi.org/10.2147/IJN.S516840
  2. Bioimpacts. 2025 ;15 30333
    Role of Toll-like receptors in exosome biogenesis and angiogenesis capacity.
    Parisa Hassanpour, Fatemeh Sadeghsoltani, Mir-Meghdad Safari, Sanya Haiaty, Reza Rahbarghazi, Ali Mota, Mohamad Rahmati.
      Adaptive inflammation consists of multiple cellular changes and molecular reactions to protect host cells against several pathological conditions. Along with the activation of varied immune cells, the production and secretion of cytokines arrays can regulate the progression of inflammatory response in a paracrine manner. Among different molecular cascades, Toll-like receptors (TLRs) are activated in response to several pathological conditions and damage signals. It has been indicated that extracellular vesicles, especially exosomes (Exos) are key bioshuttles with specific cargoes and are involved in cell-to-cell communication. The role of Exos in the initiation, progression, and cession of inflammation has been previously addressed in terms of cytokine transmission. Whether and how the activation of TLRs can alter the Exo biogenesis and angiogenesis potential in immune cells and endothelial cells (ECs) remains to be elucidated. Here, the cross-talk between the TLRs, Exo biogenesis, and angiogenesis has been highlighted.
    Keywords:  Angiogenesis; Endothelial cells; Exocytosis; Exosomes; Immune cells; Toll-like receptors
    DOI:  https://doi.org/10.34172/bi.30333
  3. J Biochem Mol Toxicol. 2025 May;39(5): e70270
    Therapeutic Potential of Exosomal miRNAs: New Insights and Future Directions.
    Haili Duan, Seyedeh Helya Siadat, Saade Abdalkareem Jasim, Pooja Bansal, Harpreet Kaur, Maytham T Qasim, Munther Kadhim Abosaoda, Raed Fanoukh Aboqader Al-Aouadi, Muath Suliman, Payam Ali Khiavi.
      Modern advancements in medicine include developing targeted drug delivery systems in the medical field, which are designed to unravel the potential of therapeutic products and overcome the barriers to the effectiveness of current approaches. Various nanopolymer carrier systems have been introduced in this regard, and the simple characteristics of extracellular vesicles have drawn special attention to their application as an effective drug delivery tool. Exosomes are very similar to transport vesicles and have a lipid-biomembrane covering an aqueous core. They also contain both hydrophilic and lipophilic substances and deliver their cargo to the desired targets. These properties enable exosomes to overcome some of the limitations of liposomes. Exosomes can easily diffuse into body fluids and remain in the bloodstream for a long time, crossing physiological barriers and entering cells. Exosomes, which contain a large volume of biomolecules, do not stimulate immune responses and do not accumulate in the liver or lungs instead of target tissues. Recent advancements in regenerative medicine have enabled scientists to utilize exosomes extracted from mesenchymal stem cells (MSCs), which possess significant regenerative abilities, for treating various diseases. The contents of these exosomes are crucial for both diagnosis and treatment, as they influence disease progression. Numerous in vitro studies have confirmed the safety, effectiveness, and therapeutic promise of exosomes in conditions such as cancer, neurodegenerative disorders, cardiovascular issues, and orthopedic ailments. This article explores the therapeutic potential of MSC-derived exosomes and outlines the essential procedures for their preparation.
    Keywords:  exosomes; extracellular vesicles; mesenchymal stem cells; miRNAs
    DOI:  https://doi.org/10.1002/jbt.70270
  4. Front Neurol. 2025 ;16 1543133
    Effects of low-intensity pulsed focal ultrasound-mediated delivery of endothelial progenitor-derived exosomes in tMCAo stroke.
    Ahmet Alptekin, Mohammad B Khan, Mahrima Parvin, Hasanul Chowdhury, Sawaiz Kashif, Fowzia A Selina, Anika Bushra, Justin Kelleher, Santu Ghosh, Dylan Williams, Emily Blumling, Roxan Ara, Asamoah Bosomtwi, Joseph A Frank, Krishnan M Dhandapani, Ali S Arbab.
       Introduction: Exosomes from different sources have been used for therapeutic purposes to target stroke and other disorders. However, exosomes from endothelial progenitor cells (EPCs) have not been tested in any stroke model, and in vivo bio-distribution study is lacking. Targeted delivery of IV-administered exosomes has been a significant challenge. Delivery of exosomes to the brain is a daunting task, and a blood-brain barrier (BBB)-penetrable peptide is being considered. However, the next step in practical treatment will be delivering naïve (unmodified) exosomes to the stroke site without destroying host tissues or disrupting BBB, or the membranes of the delivery vehicles. Low-intensity-pulsed focused ultrasound (LIPFUS) is approved for clinical use in the musculoskeletal, transcranial brain, and physiotherapy clinics. The objectives of the proposed studies were to determine whether LIPFUS-mediated increased delivery of EPC-derived exosomes enhances stroke recovery and functional improvement in mice with transient middle cerebral artery occlusion (tMCAo) stroke.
    Methods: To enhance exosome delivery to the stroke area, we utilized LIPFUS. We evaluated stroke volume using MRI at different time points and conducted behavioral studies parallel to MRI to determine recovery. Ultimately, we studied brain tissue using immunohistochemistry to assess the extent of stroke and tissue regeneration.
    Results and Discussion: In vivo, imaging showed a higher accumulation of EPC exosomes following LIPFUS without any damage to the underlying brain tissues, increased leakage of albumin, or accumulation of CD45+ cells. Groups of mice (14-16 months old) were treated with Vehicle (PBS), LIPFUS only, EPC-exosomes only, and LIPFUS+EPC-exosomes. LIPFUS + EPC exosomes groups showed a significantly decreased stroke volume on day 7, decreased FluoroJade+ cells, and significantly higher numbers of neovascularization in and around the stroke areas compared to that of other groups.
    Keywords:  exosomes; ischemic stroke; low-intensity-pulsed focused ultrasound (LIPFUS); magnetic resonance imaging (MRI); single photon emission computed tomography (SPECT)
    DOI:  https://doi.org/10.3389/fneur.2025.1543133
  5. Sci Rep. 2025 Apr 21. 15(1): 13797
    Exploring the mechanism of bone marrow mesenchymal stromal cell exosomes in respiratory syncytial virus infection based on miRNA sequencing.
    Bing Yao, Jinglei Liu, Zexiang Li, Jing Xie, Yinhe Luo, Mengqing Wang.
      The role of Bone marrow mesenchymal stem cells (BMSCs) and their exosomes in regulating the host response to viral infections has garnered significant attention, yet research on their specific mechanisms in response to respiratory syncytial virus (RSV) infection remains limited. This study analyzes changes in cytokine levels and exosomal miRNA expression profiles in BMSCs supernatants following RSV infection. The findings reveal that RSV infection leads to a significant decrease in IL-4 levels in BMSCs supernatants, alongside notable increases in IL-6, IL-12, and IFN-γ levels. Additionally, expressions of RSV F protein, G protein, and N gene were detected in the exosomes. Further in vivo experiments demonstrated that exosomes from RSV-treated BMSCs significantly enhanced the inflammatory response in RSV-infected mice, indicated by elevated serum inflammatory cytokines, lung dysfunction, airway inflammation, and increased mucus secretion. In contrast, exosomes from untreated BMSCs showed minimal effects on airway inflammation and damage in infected mice. miRNA sequencing analysis of the exosomes identified differential miRNAs enriched in multiple key signaling pathways, suggesting that RSV infection alters the functional characteristics of BMSCs exosomes, shifting their role from anti-inflammatory and repair mechanisms to a pro-inflammatory function. This transformation may be mediated by changes in the miRNA expression profile.
    Keywords:  Exosomes; High-throughput sequencing; Mesenchymal stem cells; Respiratory syncytial virus infection; miRNA
    DOI:  https://doi.org/10.1038/s41598-025-98160-3
  6. Arch Dermatol Res. 2025 Apr 19. 317(1): 729
    Exosomes as key mediators in immune and cancer cell interactions: insights in melanoma progression and therapy.
    Chou-Yi Hsu, Harish C Chandramoorthy, Jaafaru Sani Mohammed, Shaker Al-Hasnaawei, Mohammed Yaqob, Mayank Kundlas, Krishnakumar Samikan, Samir Sahoo, S K Sunori, Zainab Ahmed Abbas.
      Exosomes (30-150 nm) are small extracellular vesicles that are secreted by cells into the extracellular environment and are known to mediate cell-to-cell communication. Exosomes contain proteins, lipids, and RNA molecules in relative abundance, capable of modifying the activity of target cells. Melanoma-derived exosomes (MEXs) promote the transfer of oncogenic signals and immunosuppressive factors into immune cells, resulting in a bias of the immune response towards tumor-promoting processes. MEXs could suppress the activation and proliferation of T cells and dendritic cells and induce differentiation of myeloid-derived suppressor cells (MDSCs) and regulatory T cells (Tregs). They can induce apoptosis of antigen-specific CD8 + T cells and promote the transfer of tumor antigens, resulting in immune evasion. Specifically, MEXs can shuttle cytokines like interleukin-10 (IL-10) and transforming growth factor-β (TGF-β) to immune cells or express programmed death-ligand 1 (PD-L1 or CD274), creating an immune-suppressive microenvironment that promotes tumorigenesis. Since exosomes preferentially accumulate in melanoma tissues, this targeted delivery could enhance the bioavailability of treatments while limiting side effects. Here, we review the molecular composition of melanoma-derived exosomes, their mechanisms of action, and their potential as therapeutic targets or biomarkers in melanoma. The summarizations of these mechanisms to appropriately influence exosome-mediated interactions could yield new tactics to elicit anti-melanoma immunity or augment the therapeutic effects of current therapies.
    Keywords:  Communication; Exosome; Immune cell; MEX; Melanoma
    DOI:  https://doi.org/10.1007/s00403-025-04237-4
  7. J Spinal Cord Med. 2025 May;48(3): 527-535
    Evaluating purified exosome product and its role in neurologic and functional recovery following spinal cord injury in female rats.
    Cameron Zamanian, Chiduziem Onyedimma, F M Moinuddin, Abdul Karim Ghaith, Ryan Jarrah, Ashis Dhar, Anthony J Windebank, Mohamad Bydon.
       INTRODUCTION: Exosomes represent extracellular vesicles that mediate intercellular interactions and have been extensively studied for their therapeutic potential. Purified exosomes product (PEP) from human plasma is reported to aid in tissue repair but has never been evaluated as a potential therapy for spinal cord injury (SCI).
    OBJECTIVE: We aim to investigate the effects of PEP on axon myelination, reduction in cavity size, and functional improvements in rats following SCI.
    METHODS: Following T9-T10 laminectomy and contusion to the spinal cord, female rats received either intrathecal (IT) PEP, IT ringer-lactate solution (RL), intravenous (IV) PEP, or IV RL one day post injury. Rats underwent behavioral assessments each week for 10 weeks following SCI. After 10 weeks, histological evaluations were performed to quantity axon myelination and cavity size.
    RESULTS: The IT PEP group had significantly (P ≤ 0.05) more myelinated axons 1000 μm rostral to the injury, at the epicenter, and 1000 μm caudal of the injury (34.3 ± 3.1, 27.7 ± 2.1, and 32.0 ± 1.7, respectively) compared to the IT RL group (27.3 ± 2.5, 17.3 ± 2.5, and 23.3 ± 2.5, respectively). In addition, IT PEP rats had significantly reduced cavity size at the injury epicenter compared to controls (28.31%±1.74% vs. 34.39%±3.78%, respectively). Lastly, functional improvements were observed and sustained beginning at the 31 days following injury. The IV PEP group did not show sustained functional improvement compared to the IV RL rats.
    CONCLUSION: Our results suggest that IT PEP injection may yield beneficial effects following SCI. However, further studies are warranted to investigate the role of PEP following SCI and to optimize its potential for clinical translation.
    Keywords:  Animal models; Exosomes; Extracellular vesicles; Neural regeneration; Spinal cord injury
    DOI:  https://doi.org/10.1080/10790268.2023.2274637
  8. Stem Cell Res Ther. 2025 Apr 20. 16(1): 196
    Effects of 3D-printed exosome-functionalized brain acellular matrix hydrogel on neuroinflammation in rats following cerebral hemorrhage.
    Aobo Zhang, Boyu Sun, Chengrui Nan, Lulu Cong, Zongmao Zhao, Liqiang Liu.
       BACKGROUND: Exosome-based therapeutics have garnered significant attention for intracerebral hemorrhage (ICH) treatment due to their capacity to regulate metabolic dysregulation, restore cellular homeostasis, and modulate the injury microenvironment via bioactive cargoes such as microRNAs and proteins. However, rapid systemic clearance and enzymatic degradation critically limit their therapeutic efficacy. To address this challenge, we engineered a three-dimensional (3D) bioprinted scaffold capable of encapsulating and sustaining the release of human umbilical cord mesenchymal stem cell-derived exosomes (hUCMSC-exos).
    METHODS: Based on previous research [1-3], the scaffold was composed of a decellularized brain matrix (dECM), gelatin-methacryloyl (GelMA), and silk fibroin (SF) crosslinked with a photoinitiator. hUCMSC-exos were precisely incorporated via extrusion-based 3D bioprinting. Release kinetics were assessed via in vitro elution and in vivo imaging. An ICH rat model received stereotaxic implantation of the exosome-laden scaffold (dECM@exo). Neuroinflammatory markers (IL-6, TNF-α, IL-10) and apoptotic activity (JC-1, Annexin V/PI, TUNEL) were quantified. Neurological outcomes were longitudinally evaluated using the modified Longa scale, Bederson scoring, and sensorimotor tests (rotarod, forelimb placement) at 1, 4, 7 and 14 days post-ICH.
    RESULTS: dECM@exo demonstrated sustained exosome release over 14 days, significantly promoting neural tissue regeneration while attenuating perihematomal edema. Mechanistically, the scaffold modulated pathological MMP activity and inflammatory cytokine expression, thereby restoring extracellular matrix homeostasis and reducing neuronal apoptosis.
    CONCLUSIONS: The findings demonstrate that the 3D biological scaffold dECM@exo effectively maintains microenvironmental homeostasis in the early stages of ICH and improves outcomes associated with the condition. dECM@exo is poised to serve as a robust platform for drug delivery and biotherapy in ICH treatment, offering a viable alternative for managing this condition.
    Keywords:  3D biological scaffold; Intracerebral hemorrhage; Neuroinflammation; dECM; dECM@exo; hUCMSC-exos
    DOI:  https://doi.org/10.1186/s13287-025-04332-3
  9. Mol Cell Biochem. 2025 Apr 21.
    Exosomes secreted from adipose-derived stem cells inhibit M1 macrophage polarization ameliorate chronic endometritis by regulating SIRT2/NLRP3.
    Bin Wang, Ruizhu Yu, Zhao Zhang, Yuhong Peng, Li Li.
      Chronic endometritis (CE) is a key factor in adverse pregnancy outcomes such as miscarriage and infertility. Macrophages are an important immune cell type that secrete pro-inflammatory and anti-inflammatory cytokines that are essential for maintaining endometrial function. This study aimed to investigate the key mechanisms by which exosomes derived from adipose-derived mesenchymal stem cells (ADSCs) regulate macrophage polarization through the sirtuin 2 (SIRT2)/NOD-like receptor pyrin containing 3 (NLRP3) axis and exert a protective effect on CE. Exosomes were obtained from ADSCs (ADSCs-exo) using the classical ultracentrifugation method and characterized using transmission electron microscopy, nanoparticle tracking analysis, and western blotting. ADSCs-exo protective effects on CE mice and RAW 264.7 cells and its related molecular mechanisms were investigated using real-time quantitative polymerase chain reaction, western blotting, enzyme-linked immunosorbent assay, flow cytometry, immunofluorescence, immunoprecipitation, hematoxylin and eosin staining, and immunohistochemistry. ADSCs-exo significantly inhibited M1 macrophage polarization, as evidenced by a 54% reduction in tumor necrosis factor alfa (TNF-α), a 46% reduction in interleukin 1β (IL-1β), and a 36% reduction in interleukin 6 (IL-6) levels in LPS-induced RAW264.7 cells. In vivo, ADSCs-exo treatment reduced the expression of TNF-α by 50%, IL-1β by 58%, and IL-6 by 49% in the uterine tissues of CE mice. Moreover, ADSCs-exo upregulated the expression of SIRT2, promoted the deacetylation modification of NLRP3 to inhibit NLRP3 inflammasome activation, and further suppressed M1 macrophage polarization. However, these trends were reversed after SIRT2 silencing. Our experimental results demonstrate that ADSCs-exo alleviate CE by regulating the SIRT2/NLRP3 axis to inhibit M1 macrophage polarization. This provides a potential theoretical basis for the therapeutic role of stem cells in CE.
    Keywords:  ADSCs; Chronic endometritis; Exosomes; Macrophage polarization; NLRP3; SIRT2
    DOI:  https://doi.org/10.1007/s11010-025-05283-2
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