bims-engexo 2025-11-02 papers

bims-engexo

Biomed News

on Engineered exosomes

Issue of 2025–11–02
ten papers selected by
Ravindran Jaganathan, Universiti Kuala Lumpur

Effects and mechanisms of engineered exosomes pretreated with Scutellaria baicalensis Georgi on osteoporosis.
Current trends in exosomes as therapeutic drug delivery systems.
Advances in β-Thalassemia Gene Therapy: CRISPR/Cas Systems and Delivery Innovations.
Exosomal miR-140-3p produced by bone marrow stromal cells affects acute myeloid leukemia cell growth and apoptosis by targeting SUZ12.
RNA Therapeutics: Delivery Problems and Solutions-A Review.
Comparative Proteomics of Seminal Exosomes Reveals Size-Exclusion Chromatography Outperforms Ultracentrifugation.
Exosomes in Osteoarthritis: Breakthrough Innovations and Advanced Tissue Engineering for Cartilage Regeneration Since 2020.
Exosomes from Adipose Tissue Mesenchymal Stem Cells, a Preliminary Study for In Vitro and In Vivo Application.
Enhanced cargo of plasma alpha B crystallin in oligodendrocyte-derived exosomes accompanied by elevated expression of inflammatory factors in the temporal cortex of patients with refractory epilepsy.
Cancer-associated fibroblasts as facilitators in nasopharyngeal carcinoma progression via exosomal MMP13.

PLoS One. 2025 ;20(10): e0333897

Effects and mechanisms of engineered exosomes pretreated with Scutellaria baicalensis Georgi on osteoporosis.

Chengbin Long, Xinhang Li, Yueshen Fan, Yingkun Hu, Wenge He, Ning Hu, Fang He.

Osteoporosis (OP) is a common systemic bone disease characterized by reduced bone mineral density and the degeneration of the microstructure of bone tissue. Current therapeutic strategies for OP confront limitations including suboptimal efficacy and substantial adverse effects. This study investigates the therapeutic potential of exosomes derived from bone marrow mesenchymal stem cells (BMSCs) preconditioned with Scutellaria baicalensis Georgi (SBG) for osteoporosis management. Our findings demonstrate that SBG modulates the composition of BMSC-derived exosomes to potentiate osteogenesis. Furthermore, exosomes isolated from SBG-pretreated BMSCs (designated S-EXOs@BMSC) enhance osteogenic differentiation in MC3T3-E1 pre-osteoblasts, a process mediated by upregulating Semaphorin 3A (Sema3A). The efficacy of S-EXOs@BMSC in promoting bone regeneration was corroborated in a murine model of osteoporosis induced by ovariectomy (OVX). These results improve our understanding of how traditional Chinese medicine contributes to OP treatment and emphasize the potential of exosomes from BMSCs grown in SBG conditions as a novel therapeutic strategy for OP.

DOI: https://doi.org/10.1371/journal.pone.0333897
Naunyn Schmiedebergs Arch Pharmacol. 2025 Oct 27.

Current trends in exosomes as therapeutic drug delivery systems.

Omar Awad Alsaidan.

  Exosomes have garnered significant interest in biomedical research due to their potential therapeutic applications. They are extracellular vesicles secreted by cells, distinguished by a lipid bilayer membrane that encases various biological substances, including nucleic acids and proteins, within their lumen or lipid bilayer. They offer several advantages, like superior compatibility and targeted delivery capability, enabling innovative therapeutic development and efficient drug transport across cellular barriers, including the BBB. They also provide long circulation times, low toxicity, and protection from degradation. They play critical roles in cell communication, tissue repair, facilitating immune response, modulating inflammation, homeostasis, transferring molecules between cells, and specifically homing to tumor sites. Techniques such as microfluidic-based isolation and surface modification are advancing the production of clinical-grade exosomes. Exosomes have shown potential in delivering drugs for a wide range of diseases, including cancer, neurological disorders, infectious diseases, and cardiovascular issues. Challenges such as low yield during isolation, difficulty in large-scale production, heterogeneity of exosome populations, and maintaining stability during storage hinder their practical use. Multidisciplinary research is needed to overcome these limitations and unlock their potential in early disease detection and therapy, with future applications expected in advanced drug delivery, diagnostic biomarkers, and disease prognosis. Regulatory considerations, including rigorous preclinical and clinical trials, are crucial for translating these innovations into approved therapies. This review highlights the emerging development of exosomes in therapeutic drug delivery systems. The loading technique is discussed in a detailed manner through which the drugs are attached to exosomes and delivered to the target site.

Keywords:  Biogenesis; Drug loading; Engineered exosomes; Exosomes; Extracellular vesicles; Isolation

DOI:  https://doi.org/10.1007/s00210-025-04615-9
Cells. 2025 Oct 14. pii: 1595. [Epub ahead of print]14(20):

Advances in β-Thalassemia Gene Therapy: CRISPR/Cas Systems and Delivery Innovations.

Hongmei Liu, Peng Zhang.

  β-thalassemia is an inherited blood disorder caused by mutations in the β-globin (HBB) gene, leading to reduced or absent β-globin production, resulting in chronic anemia. While current therapies, including blood transfusions and hematopoietic stem cell transplantation, offer symptomatic relief, they are limited by complications and their limited accessibility. CRISPR-based gene editing technologies provide new therapeutic avenues by enabling the precise correction of HBB mutations or the reactivation of fetal hemoglobin (HbF) through the targeting of regulatory elements such as BCL11A. These approaches have shown promising preclinical and clinical outcomes. However, efficient and safe delivery remains a major challenge. Viral vectors offer high efficiency but raise concerns about immunogenicity and insertional mutagenesis, whereas non-viral systems such as lipid nanoparticles and engineered exosomes offer lower toxicity and modularity but face targeting limitations. This review highlights recent progress in CRISPR-based therapies for β-thalassemia and emerging delivery strategies to enhance clinical translation.

Keywords:  CRISPR gene editing; delivery systems; fetal hemoglobin induction; hematopoietic stem cells; β-thalassemia

DOI:  https://doi.org/10.3390/cells14201595
Leuk Res. 2025 Oct 16. pii: S0145-2126(25)00612-5. [Epub ahead of print]159 108122

Exosomal miR-140-3p produced by bone marrow stromal cells affects acute myeloid leukemia cell growth and apoptosis by targeting SUZ12.

Jiajia Li, Feifan Li, Mengmeng Zhang, Yanping Wu, Meng Wang, Pingping Zhang.

  There is growing evidence that exosomes produced by bone marrow stromal cells (BMSCs) are associated with the progression of several cancers, including acute myeloid leukemia (AML), but intrinsic molecular mechanisms remain elusive. Here, we applied previous microarray analysis (GSE133276 and GSE209871) to identify differentially expressed exosomal miRNAs in BMSCs of AML patients, and candidate miR-140-3p, miR-142-5p and miR-142-3p were selected. This study aimed to investigate whether BMSCs affects AML progression are mediated by the candidates, and to explore regulatory mechanisms. The levels of the candidates were examined in bone marrow and BMSCs from AML patients, and exosomes from BMSCs of normal subjects and AML cells by qRT-PCR. Cell proliferation and apoptosis of AML cells co-cultured with BMSCs were detected through CCK-8, colony formation, flow cytometry, and Caspase-3 activity assays with manipulation of the candidate miRNAs expression. RNA pull-down and luciferase reporter assays to identify the downstream target mRNAs of the miRNAs. We confirmed that miR-140-3p, miR-142-5p and miR-142-3p levels were downregulated in bone marrow and BMSCs of AML patients, and were significantly enriched in exosomes of BMSCs but not AML cells. BMSCs co-cultured with AML cells could transfer these miRNAs into AML cells, and suppressed the proliferative potential and promoted the apoptotic behavior of AML cells. Furthermore, miR-140-3p agomir in BMSCs exacerbated the effects of the co-culture system on the AML cell proliferation and apoptosis, which were attenuated by miR-140-3p antagomir. In contrast, co-culture data showed that miR-142-5p and miR-142-3p had no significant effect on cell proliferation and apoptosis. Moreover, SUZ12 polycomb repressive complex 2 subunit (SUZ12) was directly targeted by miR-140-3p, overexpression or inhibition of SUZ12 in AML cells partially counteracted miR-140-3p agomir or antagomir-mediated cellular effects, respectively. Our study suggested that the BMSCs-derived exosomal miR-140-3p, rather than miR-142-5p and miR-142-3p, has a regulatory effect on the growth and apoptosis of AML cells by targeting SUZ12.

Keywords:  AML; BMSCs; Exosomes; MiR-140–3p; SUZ12

DOI:  https://doi.org/10.1016/j.leukres.2025.108122
Pharmaceutics. 2025 Oct 07. pii: 1305. [Epub ahead of print]17(10):

RNA Therapeutics: Delivery Problems and Solutions-A Review.

Natalia Pozdniakova, Evgenii Generalov, Alexei Shevelev, Olga Tarasova.

  RNA-based therapeutics offer transformative potential for treating devastating diseases. However, current RNA delivery technologies face significant hurdles, including inefficient tissue targeting, insufficient selectivity, and severe side effects, leading to the termination of many clinical trials. This review critically assesses the landscape of RNA-derived medicines, examining world-renowned mRNA vaccines (Spikevax, BNT162b2/Comirnaty) and RNA-based therapeutics like Miravirsen (anti-miR-122). It details the composition and clinical trial results of numerous modified short RNA drugs (e.g., siRNAs, miRNA mimetics/inhibitors) targeting various conditions. Prospects for RNA-based medicines are analysed for diseases with substantial societal impact, such as cancer, autoimmune disorders, and infectious diseases, with a focus on evolving delivery methods, including lipid nanoparticles, viral vectors, and exosomes. RNA-mediated macrophage reprogramming emerges as a promising strategy, potentially enhancing both delivery and clinical efficacy. This review highlights that while approved RNA therapies primarily target rare diseases due to delivery limitations, novel approaches in RNA modification, targeted delivery systems, and enhanced understanding of molecular mechanisms are crucial for expanding their application to prevalent diseases and unlocking their full therapeutic potential.

Keywords:  AAV vectors; RNA; RNA mimetic; RNA vaccine; exosomes; lipid nanoparticles; macrophage reprogramming; viral vectors

DOI:  https://doi.org/10.3390/pharmaceutics17101305
Biomedicines. 2025 Oct 09. pii: 2459. [Epub ahead of print]13(10):

Comparative Proteomics of Seminal Exosomes Reveals Size-Exclusion Chromatography Outperforms Ultracentrifugation.

Ajaya K Moharana, Manesh Kumar Panner Selvam, Soumya Ranjan Jena, Partha K Chandra, David W Busija, Luna Samanta, Suresh C Sikka.

  Background: Extracellular vesicles, particularly exosomes, play a crucial role in cell-cell communication and as carriers of biomarkers. However, their use in clinical settings is limited due to a lack of standardized isolation and characterization. Ultracentrifugation (UC) is considered a gold standard for exosome isolation but presents several limitations. Size-exclusion chromatography (SEC) has recently gained attention as a superior method, which offers better yield, purity, and protection of exosome physical properties. This study focused on optimizing the SEC method for isolation of exosomes from seminal plasma and comparing yield, quality, and proteome profiles with those obtained by UC. Methods: In this SEC method, seminal plasma (0.5 mL) was loaded onto a SEC column and collected in 13 fractions of 0.4 mL each. The physical and molecular characterization of exosomes was carried out using a ZetaView analyzer and Western blot, respectively. Further, SEC-isolated exosomes were used for proteomic profiling and functional bioinformatic analysis. Results: The second and third fractions had the highest concentration of exosomes with uniform size and strong expression of exosome markers. Also, comparative proteomic analysis identified 3315 proteins in SEC-isolated exosomes and 931 in UC-isolated exosomes, with 709 proteins in common. SEC-isolated exosomes showed greater overlap with Vesiclepedia's and ExoCarta's top 100 lists than UC-isolated exosomes (Vesiclepedia: 91 vs. 77 proteins, ExoCarta: 94 vs. 79). Proteins from SEC- and UC-isolated exosomes showed similar enrichment profiles across all three gene ontology categories. Conclusions: Overall, this optimized SEC protocol is a reliable alternative method to isolate seminal exosomes with high purity, supporting its potential applications in clinical and basic research.

Keywords:  exosomes; extracellular vesicles; proteomic profiling; seminal plasma; size-exclusion chromatography (SEC)

DOI:  https://doi.org/10.3390/biomedicines13102459
Biomedicines. 2025 Oct 13. pii: 2486. [Epub ahead of print]13(10):

Exosomes in Osteoarthritis: Breakthrough Innovations and Advanced Tissue Engineering for Cartilage Regeneration Since 2020.

Xiao-He Yang, Shu-Yin Chen, Quan-Fa Zhou, You-Zhi Cai.

   BACKGROUND/OBJECTIVES: Osteoarthritis (OA) is a prevalent age-related degenerative joint disease causing cartilage damage, leading to a debilitating lifestyle. However, there are currently no drugs on the market that promote cartilage repair, and advanced cases often require arthroplasty. Increasing evidence suggests that exosomes, the smallest extracellular vesicles (30-150 nm) secreted by all cell types, are involved in the pathological process of OA and play a crucial and complex role in its progression. This review aims to provide in-depth insights into exosome biology, isolation techniques, their role in OA pathophysiology, and their clinical therapeutic potential.
METHODS: We systematically reviewed studies published since 2020 on exosomes in OA, focusing on their biological properties, isolation techniques, pathological roles, and therapeutic applications.
RESULTS: Exosomes derived from synovial fluid, chondrocytes, synoviocytes, and mesenchymal stem cells regulate key processes in OA progression, including inflammation, apoptosis, extracellular matrix degradation, and regeneration. Various cell-derived exosomes show therapeutic potential for cartilage damage/OA. However, their mechanisms of action have not been fully investigated. Moreover, emerging methodologies, such as utilizing novel materials for exosome delivery, potentially facilitate the development of more effective and personalized therapeutic interventions.
CONCLUSIONS: Exosomes exert dual roles in OA pathogenesis and therapy. Although challenges remain regarding their sources, dosage, delivery, and standardization, exosome-based strategies represent a promising cell-free therapeutic approach with potential applications in personalized and precision medicine.

Keywords:  OA therapy; cartilage regeneration; exosome modification; stem cells; tissue engineering

DOI:  https://doi.org/10.3390/biomedicines13102486
Bioengineering (Basel). 2025 Oct 21. pii: 1129. [Epub ahead of print]12(10):

Exosomes from Adipose Tissue Mesenchymal Stem Cells, a Preliminary Study for In Vitro and In Vivo Application.

Thao Duy Huynh, Ciro Gargiulo Isacco, Quan Thai Minh Ngo, Binh Thanh Nguyen, Tuan Ngoc Huu Nguyen, Tri Minh Dang Bui, Vinh Minh Ngo, Ky Quoc Truong, Tro Van Chau, Hoa Cong Truong, Kieu Diem Cao Nguyen, Emilio Jirillo, Van Hung Pham, Luigi Santacroce, Toai Cong Tran.

  Mesenchymal stem cells (MSCs), particularly their secreted exosomes, small microvesicles, represent a major focus in regenerative medicine due to their therapeutic potential. Exosomes exhibit growth factors and cytokines and are loaded with microRNAs (miRNA) and short interfering RNA (siRNA) that can be transferred to other cells, potentially affecting their function. Exosomes are crucial mediators of intercellular communication, are immunomodulatory, and are promoters of tissue regeneration. Despite their promise, the standardized methods for exosome isolation and characterization remain weak. This exploratory study addresses this gap by detailing an effective method for isolating exosomes from adipose tissue mesenchymal stem cells (AT-MSCs), emphasizing precipitation as a technique yielding a high efficiency and purity compared to other methods. Functionally, we aimed to confirm the AT-MSC exosomes' ability to exert an effective protective activity on the skin and its main components, such as fibroblasts, collagen, and elastin. To achieve this goal, we had to demonstrate that AT-MSC exosomes are safe and free of toxic substances. They can express specific proteins such as CD9, CD63, and CD81, which are well-known exosome markers. These exosomes also contain key miRNAs, including miRNA-203 A, miRNA-203 B, and miRNA-3196, important for skin regeneration, as well as enhancers of cell integrity and proliferation. We eventually confirmed the ability of exosomes to exert protective and recovery effects on fibroblasts after H2O2-induced damage in vitro, as well as on mouse skin after UVB-induced damage in vivo. These effects were verified by measuring levels of reactive oxidative species (ROS), assessing SA-β-Galactosidase (SA-β-Gal) activity, analyzing the cell cycle, evaluating the telomere length of fibroblasts by RT-PCR, and conducting histological assessments of collagen and elastin structure in murine skin after UVB exposure. This exploratory work provides valuable insights into the isolation, characterization, and bioactive and reparative properties of exosomes from AT-MSCs, supporting their development for future studies and therapeutic applications.

Keywords:  H2O2-induced damage; UVB-induced damage; adipose tissue mesenchymal stem cells (AT-MSCs); exosomes; miRNA; qRT-PCR; siRNA

DOI:  https://doi.org/10.3390/bioengineering12101129
Biochim Biophys Acta Mol Basis Dis. 2025 Oct 29. pii: S0925-4439(25)00446-6. [Epub ahead of print] 168096

Enhanced cargo of plasma alpha B crystallin in oligodendrocyte-derived exosomes accompanied by elevated expression of inflammatory factors in the temporal cortex of patients with refractory epilepsy.

Xiaoshuai Ji, Dongyan Wu, Yongsheng Xie, Ming Chen, Zengxin Qi, Nan Zhou.

   PURPOSE: Plasma exosomes have emerged as key mediators of communication between neural cells and the periphery, playing pivotal roles in various neurological diseases. However, their involvement in the pathogenesis of epilepsy remains unclear. This study aimed to investigate the expression of alpha B crystallin (CRYAB) in plasma exosomes and the temporal cortex as a potential contributor to epileptogenesis.
METHODS: The study included 112 participants, comprising patients with refractory medial temporal lobe epilepsy, glioma patients with and without pre-operative epilepsy, and age- and sex-matched healthy controls. Plasma exosomes were isolated from peripheral blood using immuno-co-precipitation and resin antibody techniques. Exosome morphology and size distribution were evaluated using transmission electron microscopy and nanoparticle tracking analysis. Neuron- or glia-derived exosomes were enriched through antibody-based immunoabsorption. Plasma CRYAB levels were quantified using an enzyme-linked immunosorbent assay. CRYAB expression in neurons and glia of the human temporal cortex was evaluated by immunocytochemistry. Western blotting was performed to detect the expression levels of CRYAB and inflammatory cytokines in brain tissue.
RESULTS: Isolated circulating exosomes were confirmed to be partially derived from the central nervous system (CNS), as evidenced by the presence of neuronal and glial markers. CRYAB was highly expressed in exosomes derived from oligodendrocytes. Patients with epilepsy exhibited significantly elevated levels of plasma oligodendrocyte-derived exosomal CRYAB compared to healthy controls. This was paralleled by increased expression of CRYAB in the temporal cortex of patients with epilepsy, indicating CNS origin of the exosomal cargo. A negative correlation between plasma CRYAB levels and oligodendrocyte-derived exosomal CRYAB was observed in both controls and epileptic patients. Furthermore, patients with epilepsy demonstrated significantly higher density of CRYAB immunoreactivity in temporal cortex oligodendrocytes. The temporal cortex of patients with refractory epilepsy exhibited a significant upregulation of CRYAB, concomitant with elevated levels of inflammatory cytokines.
CONCLUSION: The finding that plasma oligodendrocyte-derived exosomal CRYAB is upregulated in patients with epilepsy highlights a potential role of oligodendrocyte-secreted CRYAB in its pathogenesis.

Keywords:  Crystallin; Inflammatory factors; Intractable epilepsy; Oligodendrocyte exosome

DOI:  https://doi.org/10.1016/j.bbadis.2025.168096
Transl Cancer Res. 2025 Sep 30. 14(9): 5838-5852

Cancer-associated fibroblasts as facilitators in nasopharyngeal carcinoma progression via exosomal MMP13.

Haijuan Xiao, Mengdie You, Lixiao Xie, Yingyu Zhang, Zhenxin Zhang, Ziyu Zhu, Qicheng Zhang.

   Background: Cancer-associated fibroblasts (CAFs), essential components of the tumor microenvironment (TME), contribute to tumor formation. Our previous research demonstrated that exosomes containing matrix metalloproteinase 13 (MMP13) accelerate metastasis in nasopharyngeal carcinoma (NPC). This study aimed to determine whether exosomes containing MMP13 promote NPC development by stimulating the differentiation of normal fibroblasts (NFs) into CAFs.
Methods: The presence of CAFs in NPC was identified through immunohistochemistry (IHC) analysis. NPC cells activated NFs into CAFs, according to the co-culture cell model. Exosomes were characterized by Western blot and electron microscopy analysis. NFs were treated with exosomes, and Western blot, migration, and 5-ethynyl-2'-deoxyuridine (EdU) assays were conducted to assess CAFs activation. Western blot analysis was used to assess whether exosomes derived from CAFs activated the Notch signaling pathway in human low-differentiated nasopharyngeal carcinoma cell line (CNE2). The effect of MMP13 on exosomes generated from CAFs in vivo was verified using a nude mouse model, and the effect of MMP13 on the immune microenvironment of CAFs in vivo was verified using the C57BL/6 mouse model.
Results: We found that NPC cells, after converting NFs to CAFs, exhibited enhanced proliferative and migratory capacities. NPC cells secreted MMP13 containing exosomes, which facilitated the conversion. The secretion of exosomes by activated CAFs has been demonstrated to promote tumor progression by activating the Notch signaling system, promoting angiogenesis, and suppressing T cell immunity. The inhibition of exosome MMP13 has the potential to impede the migration and proliferation of recipient cells. Inhibition of exosomal MMP13 may suppress recipient cell migration and proliferation.
Conclusions: Our research identified a critical mechanism in which MMP13-rich exosomes from NPC cells may influence the development of CAFs in the TME, while the exosomes produced by CAFs further support the malignant development of NPC.

Keywords:  Nasopharyngeal carcinoma (NPC); cancer-associated fibroblasts (CAFs); exosomes; matrix metalloproteinase 13 (MMP13); microenvironment

DOI:  https://doi.org/10.21037/tcr-2025-428