bims-engexo 2026-01-18 papers

bims-engexo

Biomed News

on Engineered exosomes

Issue of 2026–01–18
eleven papers selected by
Ravindran Jaganathan, Universiti Kuala Lumpur

Recent Advances in the Application of Engineered Extracellular Vesicles from mesenchymal stem cells for Traumatic Central Nervous System.
Dental mesenchymal stem cell-derived exosomes for oral diseases: Classification, functionalization and clinical prospects.
Duo-nano exosome encapsulating hydrogel boosts wound healing across xenogenic and allogenic models.
Exosome-Based Cartilage-Targeted Delivery System: Strategies and Applications.
Exosome encapsulated albumin nanoparticles target delivery of DBET6 as a treatment for triple-negative breast cancer.
[Exosomes from folic acid-treated subpatellar fat pad-derived mesenchymal stem cells promote M2 polarization of macrophages in vitro].
3D-printed scaffold loaded with baicalin exosomes promotes bone defect repair via mediating PRRX2 to alleviate inflammation.
M1 Macrophage-Engineered Vesicles Have Anti-Cancer Activity in Ovarian Cancer.
Mesenchymal stromal cell-derived extracellular vesicles in regenerative medicine: Standardisation, bioengineering and clinical translation.
Olfactory Mucosa Mesenchymal Stem Cell-Derived Exosomal lncRNA RMRP Regulates Glial Metabolic Reprogramming to Promote Axonal Regeneration After Spinal Cord Injury by Inhibiting WTAP-Mediated p53 m6A.
Incorporation of Functional Proteins on Cellular Surfaces via Artificial Cell-Derived Vesicles (ACDVs) for Plasma Membrane Reprogramming.

Eur J Pharmacol. 2026 Jan 09. pii: S0014-2999(26)00018-X. [Epub ahead of print] 178536

Recent Advances in the Application of Engineered Extracellular Vesicles from mesenchymal stem cells for Traumatic Central Nervous System.

Mahdi Ahmadi, Aileen Saranjam, Mohammad Hamidifar, Maryam Shoaran, Jafar Rezaie.

  Traumatic injuries to the central nervous system (CNS), including traumatic brain injury (TBI) and spinal cord injury (TSCI), are among the leading causes of disability and mortality worldwide. The valuable effect of extracellular vesicles (EVs) from mesenchymal stem cells (MSCs-EVs) in the treatment of traumatic injuries has been documented. EVs, including exosomes, are heterogeneous cell-derived particles, contributing to cell communication through exchanging biomolecules between cells. MSCs-EVs can regulate physiological processes, including synaptic plasticity, neuronal firing, development and repair of myelin sheath, neuroprotection, advancement of neuroinflammation, and extent and elimination of protein aggregates. However, natural MSCs-EVs have some limitations. Recent advancements have emerged that enable MSCs-EVs to be engineered for effective and targeted therapy in traumatic injuries. Most experiments have focused on miRNA-engineered MSCs-EVs to boost their therapeutic effects. In TBI models, MSCs-EVs have been modified to deliver miR-124, miR-17-92, miR-124-3p, or BDNF, whereas in TSCI models, EVs have been engineered with miR-216a-5p, miR-146a-5p, miR-133b, miR-146, miR-138-5p, miR-29b, miR-181c, lncGm37494, siRNAs, or Shh. Results from in vitro and animal studies show the substantial potential of engineered MSCs-EVs for protection, neuroregeneration, and functional recovery. But challenges remain in translating these outcomes into clinical trials, including standardization, safety, and delivery efficacy. In this review, we summarize recent knowledge on MSCs-EVs, focusing on their mechanisms of action in CNS traumatic injuries, and discuss the latest developments, inherent advantages, and potential hurdles in evolving these groundbreaking therapeutic approaches.

Keywords:  Central nervous system; Exosomes; Extracellular vesicles; Mesenchymal stem cells; Traumatic injuries

DOI:  https://doi.org/10.1016/j.ejphar.2026.178536
Colloids Surf B Biointerfaces. 2026 Jan 08. pii: S0927-7765(26)00019-6. [Epub ahead of print]261 115431

Dental mesenchymal stem cell-derived exosomes for oral diseases: Classification, functionalization and clinical prospects.

Yuxuan Teng, Qijing Yang, Yang Zhao, Lingao Zhu, Bingwen Zhong, Bowei Wang, Zhihui Liu.

  The conventional therapeutic approaches for oral diseases primarily encompass dental restoration, pulp therapy, and maxillofacial surgical interventions. However, these methods are difficult to promote tissue regeneration and immune regulation. Mesenchymal stem cell-derived exosomes (MSC-Exos), mainly derived from tissues such as bone marrow, umbilical cord blood, umbilical cord, placenta, and fat, have been used to study the treatment of oral diseases. Conventional MSCs-Exos have relatively low immunogenicity and ethical issues, but exosomes derived from dental mesenchymal stem cells (DSCs) not only have abundant sources but also lower immunogenicity, which can circumvent ethical restrictions. This review aims to comprehensively investigate the isolation and characterization methods of exosomes derived from dental-derived mesenchymal stem cells (DSC-Exos) as well as their sources and biological properties. It further reviews recent advances in their application within the field of stomatology and summarizes various material-based delivery systems for exosomes. Particular emphasis is placed on their therapeutic potential in inflammatory conditions such as pulpitis, periodontitis, temporomandibular joint disorders, and immune-related diseases, as well as the application prospects of inducing cell directional differentiation in pulp-dentin complex regeneration, jawbone repair, and soft tissue regeneration. In addition, we have reviewed here some possible applications of DSC-Exos to prevent orthodontic relapse and treat oral cancer. The DSC-Exos play multiple roles, including anti-inflammatory activity, immunomodulatory effect, and tissue regeneration, and have a great potential in the clinical treatment of oral inflammation, tissue defects, and immune dysregulation. Their therapeutic efficacy could also be improved by combining them with other biomaterials.

Keywords:  Delivery system; Dental mesenchymal stem cell-derived exosomes; Isolation and characterization; Oral diseases; Tissue regeneration

DOI:  https://doi.org/10.1016/j.colsurfb.2026.115431
Biomaterials. 2025 Dec 27. pii: S0142-9612(25)00873-7. [Epub ahead of print]329 123953

Duo-nano exosome encapsulating hydrogel boosts wound healing across xenogenic and allogenic models.

Bibi S Subhan, Sydney E Hanson, Dianny Almanzar, Juan F Cortes Troncoso, Priya Katyal, Jonathan W Sun, Hao-Wei Shih, Tamara Mestvirishvili, Michael Meleties, Fernando Arias, Andrew Wang, Kelly Ruggles, Igor Dolgalev, Paolo Mita, Jin Kim Montclare, Piul S Rabbani.

Chronic wounds, especially in diabetic patients, pose a significant clinical challenge due to impaired microvasculature and delayed healing. This study presents Exo-Q, a novel thermoresponsive hydrogel formed by co-gelation of engineered Q protein nanofibers with exosomes, a class of vesicular intercellular communication mediators. Exo-Q transitions from a gel to a viscoelastic solution at physiological temperature, enabling localized, topical delivery of exosomes with an initial burst release followed by sustained release. In a diabetic mouse wound model, Exo-Q effectively delivered human bone marrow multipotent stromal cell-derived exosomes directly to the wound bed, where they accumulated in endothelial cells of granulation tissue without detectable systemic distribution. Exosomes produced under stringent and replicable cell culture conditions consistently carried biomacromolecular cargo enriched for miRNAs with validated targets in angiogenesis-associated genes, indicative of their therapeutic potential. Topical application of Exo-Q resulted in extensive neovascularized granulation tissue, significantly accelerating wound closure to levels comparable to non-diabetic wounds. Importantly, the hydrogel's modular design maintained the functional integrity of Q protein nanofibers and exosomes, demonstrating compatibility with full-thickness human wounds. This platform allows for tailored customization to address critical stages of diabetic wound healing while ensuring efficacy at low dosages, potentially enabling patient-administered treatment. By leveraging advanced biomaterials, Exo-Q advances the therapeutic efficacy of exosome-based interventions for diabetic wounds, offering a localized, non-invasive solution to chronic, non-healing wounds. This innovative hydrogel platform represents a modular therapeutic strategy with significant potential for clinical applications in regenerative medicine.

DOI: https://doi.org/10.1016/j.biomaterials.2025.123953
Small Sci. 2026 Jan;6(1): e202500436

Exosome-Based Cartilage-Targeted Delivery System: Strategies and Applications.

Yao Wang, Bo Chen, Haodong Zhu, Zhenyu Sun.

  With the ageing of the global population, cartilage-related diseases, such as osteoarthritis (OA) and intervertebral disc degeneration (IVDD), have increasingly become significant social problems threatening human health. Therefore, targeted therapy for cartilage is becoming more and more promising. Exosomes, natural cellular derivatives, have emerged as promising therapeutic vectors owing to their inherent biocompatibility, superior biomatrix penetration capabilities, and therapeutic efficacy in cartilage regeneration. Precise targeting of cartilage tissues can be achieved through specific construction strategies, showing potential for treating cartilage-related diseases. However, a review of cartilage-targeted exosomes is still lacking. Previous studies have merely categorized chondrocytes under the broader group of osteocytes, regarding them only as a supplementary component of bone-targeted therapy, or have been limited to a single modification technique. This review specifically focus on cartilage-targeted exosomes, systematically integrating two modification methods-direct surface modification and parental cell engineering-and highlights translational applications in disease contexts. This article elaborates in detail on the construction strategies of cartilage-targeted exosomes and explores their application progress in related diseases such as OA and IVDD, aiming to provide a reference for further research and clinical translation in this field.

Keywords:  cartilage‐targeted delivery; exosome; intervertebral disc degeneration; osteoarthritis; rheumatoid arthritis

DOI:  https://doi.org/10.1002/smsc.202500436
PLoS One. 2026 ;21(1): e0335890

Exosome encapsulated albumin nanoparticles target delivery of DBET6 as a treatment for triple-negative breast cancer.

Han Yu, Jingyuan Zhao, Dan Wu, Hong Yuan.

Triple-negative breast cancer (TNBC) is a highly aggressive disease with significant mortality, and there is an urgent need for therapies that can effectively target the disease and enhance patient survival rates. The BET family protein BRD4 plays a key role in the development and progression of TNBC. Its degrader, dBET6-a proteolysis-targeting chimera (PROTAC) molecule-shows promising anti-tumor potential but suffers from low bioavailability and poor tissue selectivity. To improve its targeted delivery efficiency, this study developed a novel nanodrug delivery system, Exo-BSA@dBET6, which encapsulates dBET6 within bovine serum albumin (BSA) nanoparticles and further coats them with milk-derived exosomes, leveraging both the natural targeting ability of exosomes and the high drug-loading capacity of BSA. The results demonstrated that Exo-BSA@dBET6 has a uniform particle size of approximately 85.89 nm, good stability, high encapsulation efficiency, and excellent biocompatibility. In vitro experiments showed that this nanosystem significantly enhanced the cellular uptake of the drug in MDA-MB-231 cells, primarily through clathrin-mediated endocytosis, and exhibited efficient lysosomal escape. Compared to free dBET6 and BSA@dBET6, Exo-BSA@dBET6 displayed stronger cytotoxicity, significantly induced apoptosis, increased reactive oxygen species (ROS) levels, reduced mitochondrial membrane potential, and up-regulated caspase-3 protein expression. Western blot analysis further confirmed that Exo-BSA@dBET6 effectively degraded BRD4 protein, down-regulated c-Myc, and up-regulated Bax expression. Transcriptome sequencing analysis indicated that the nanosystem exerts anti-tumor effects by modulating key signaling pathways such as PI3K-Akt and Rap1. This study successfully constructed an exosome-modified albumin-based nanodrug delivery system that significantly enhances the targeting and anti-TNBC efficacy of dBET6, providing a new strategy for the targeted therapy of TNBC.

DOI: https://doi.org/10.1371/journal.pone.0335890
Nan Fang Yi Ke Da Xue Xue Bao. 2026 Jan 20. pii: 1673-4254(2026)01-0166-09. [Epub ahead of print]46(1): 166-174

[Exosomes from folic acid-treated subpatellar fat pad-derived mesenchymal stem cells promote M2 polarization of macrophages in vitro].

Zhe Wang, Keyu Kong, Minghao Jin, Sonu Ng, Wenxuan Fan, Zanjing Zhai, Zihao Hu, Lin Niu, Yansong Qi, Yongsheng Xu.

   OBJECTIVES: To evaluate the effect of exosomes derived from folic acid (FA)-treated infrapatellar fat pad mesenchymal stem cells (IPFP-MSCs) on M1 and M2 polarization of macrophages in vitro.
METHODS: Infrapatellar fat pad tissues were obtained from surgical patients without knee osteoarthritis to isolate IPFP-MSCs. The exosomes were extracted from the cell cultures with or without FA treatment and identified by transmission electron microscopy, TEM, NTA and Western blotting. RAW264.7 cells were induced with lipopolysaccharide (LPS) and incubated with exosomes from FA-treated or untreated IPFP-MSCs for 12 h, and Exos uptake was observed using confocal microscopy. The changes in expression levels of IL-1β, IL-6, TNF-α, iNOS, ARG1, MRC1, and CD206 in the macrophages were detected using qRT-PCR, ELISA, flow cytometry and immunofluorescence staining.
RESULTS: The exosomes derived from IPFP-MSCs showed a typical cup shape, were positive for CD9 and CD81, and could be uptaken by macrophages. In LPS-induced macrophages, incubation with exosomes from FA-treated IPFP-MSCs significantly decreased the expressions of IL-1β, IL-6, TNF‑α, and NOS2, and increased the expressions of ARG1 and MRC1. Treatment of the macrophages with exosomes from FA-treated IPFP-MSCs significantly lowered CD86-positive cell percentage, increased CD206-positive cells and the CD206/CD86 ratio, lowered cellular expression of iNOS, and enhanced the expression of CD206.
CONCLUSIONS: Exosomes from FA-treated IPFP-MSCs promotes M2 polarization of macrophages more effectively than exosomes from unmodified IPFP-MSCs, suggesting a new exosome modification strategy for targeted treatment of knee osteoarthritis.

Keywords:  exosomes; folic acid; macrophage; mesenchymal stem cells; osteoarthritis

DOI:  https://doi.org/10.12122/j.issn.1673-4254.2026.01.18
iScience. 2026 Jan 16. 29(1): 113565

3D-printed scaffold loaded with baicalin exosomes promotes bone defect repair via mediating PRRX2 to alleviate inflammation.

Haotian Zhu, Kai Cheng, Mingwei Tian, Yuanhao Peng, Yadi Zhang, Han Yan, Shaoxing Fan, Bo Shang, JiaYi Wu, Huanwen Ding, Naru Zhao.

  Chronic nonunion of bone defects remains a significant challenge in orthopedic treatment. Artificial bone graft materials are expected to solve this problem due to their suitable degradation rate and good osteoconductivity. However, ROS and inflammation within the defect environment are important causes of implant failure. Exosomes derived from different preconditioned bone mesenchymal stem cells (BMSCs) have shown great potential in the treatment of various diseases. Here, we developed a 3D-β-TCP@BA-BMSC-exos scaffold that loaded baicalin-pretreated BMSC exosomes (BA-BMSC-exos) on a 3D-printed β-tricalcium phosphate scaffold (3D-β-TCP) for bone defect repair. In vitro experiments showed that BA-BMSC-exos enhanced proliferation, migration, and tube formation in HUVECs, as well as inhibited inflammation via mediating PRRX2. Moreover, 3D-β-TCP scaffolds loaded with BA-BMSC-exos clearly alleviated inflammation and promoted angiogenesis in a calvarial defect rat model. This study suggests that 3D-β-TCP scaffolds combined with BA-BMSC-exos are a promising strategy to enhance bone repair and regeneration.

Keywords:  Biological sciences; Engineering

DOI:  https://doi.org/10.1016/j.isci.2025.113565
Cancer Nanotechnol. 2025 Dec;pii: 35. [Epub ahead of print]16(1):

M1 Macrophage-Engineered Vesicles Have Anti-Cancer Activity in Ovarian Cancer.

Connie D Cao, J Robert McCorkle, Derek B Allison, Donglin Yan, Kristen Hill, Lan Li, Rani Jayswal, David Schweer, Charles S Dietrich, Frederick R Ueland, Christopher I Richards, Jill M Kolesar.

   Background: Ovarian cancer typically presents at an advanced stage, has a poor prognosis, and is a leading cause of cancer-related deaths in women. Extracellular vesicles (EVs) are cell membrane derived nanoparticles that function in specific cell-to-cell communication and are under development as novel drug delivery vehicles and modulators of the tumor microenvironment. Artificial cell-derived vesicles (ACDVs) from M1 macrophages are able to repolarize macrophages from a M2 to a M1 phenotype and target tumor cells in in vitro studies.
Results: In this study, we generated engineered EVs (EEVs) by membrane disruption of M1 macrophages (MEVs) with and without cisplatin to generate cisplatin-loaded MEVs (C-MEVs) and empty MEVs (E-MEVs), which we tested in an ovarian cancer mouse xenograft model. E-MEVs and C-MEVs exhibited significantly less weight loss and equivalent activity to cisplatin, with improved activity over controls.
Conclusions: Further development of MEVs for the treatment of ovarian cancer is warranted.

Keywords:  engineered vesicles; extracellular vesicles; immunotherapy; ovarian cancer

DOI:  https://doi.org/10.1186/s12645-025-00337-y
Regen Ther. 2026 Mar;31 101058

Mesenchymal stromal cell-derived extracellular vesicles in regenerative medicine: Standardisation, bioengineering and clinical translation.

Yusuke Shimizu, Yoshikazu Inoue, Naoki Matsuura, Tatsuya Ishii, Yoshihiro Sowa, Hiroshi Sunami, Edward Hosea Ntege.

  Mesenchymal stromal cell-derived extracellular vesicles (MSC-EVs) have emerged as promising cell-free therapeutics that recapitulate key paracrine functions of MSCs whilst mitigating limitations of viable-cell therapies. Clinical translation is hindered by inconsistent dose metrics, lack of validated potency assays, and manufacturing complexities. Here we review advances in MSC-EV standardisation, source and culture determinants, engineering and delivery platforms, and clinical applications, exemplified by chronic wound healing. We operationalise dual-metric dosing (particles plus protein) linked to mechanism-aligned potency assays, adopt a route-aware exposure-response framework to guide delivery strategies, and propose decision matrices aligning MSC sources and bioprocesses with indication-specific tasks. Good Laboratory Practice safety panels and Good Manufacturing Practice scale-up strategies are outlined to support regulatory readiness. Early clinical studies demonstrate feasibility and short-term safety but reveal heterogeneous efficacy, underscoring the need for harmonised dosing and potency measures. Collectively, these insights provide a roadmap to advance MSC-EVs as indication-matched regenerative medicines.

Keywords:  Bioengineering and biomaterials; Clinical translation; Dose metrics and potency assays; GMP manufacturing and comparability; Mesenchymal stromal cell–derived extracellular vesicles; Pharmacokinetics and biodistribution

DOI:  https://doi.org/10.1016/j.reth.2025.101058
FASEB J. 2026 Jan 31. 40(2): e71461

Olfactory Mucosa Mesenchymal Stem Cell-Derived Exosomal lncRNA RMRP Regulates Glial Metabolic Reprogramming to Promote Axonal Regeneration After Spinal Cord Injury by Inhibiting WTAP-Mediated p53 m6A.

Chuang Wang, Jiangshan Zhang, Danting Zeng, Pengcheng Chen, Weimin Chen, Ying Xia.

  Glial metabolic reprogramming is essential for axonal regeneration post-spinal cord injury (SCI). While olfactory mucosa mesenchymal stem cell-derived exosomal lncRNA RMRP (OM-MSC-exo-RMRP) exhibits therapeutic potential for SCI, its involvement in glial metabolic reprogramming requires elucidation. OM-MSC-derived exosomes (OM-MSC-exos) were extracted and identified. Astrocytes (CTX-TNA2) were stimulated with TNF-α, treated with OM-MSC-exos, and co-cultured with dorsal root ganglion neuron (DRGns) to model glia-neuron interactions. DRGn axonal regeneration was assessed using immunofluorescence staining and western blotting. Astrocyte metabolism was assessed by detecting ECAR, OCR, glucose consumption, lactate production, and LDH activity. Molecular interactions among RMRP, WTAP, and p53 were determined by qPCR, western blotting, RNA immunoprecipitation, MeRIP-qPCR, and actinomycin D assays. A SCI mouse model was built and administered OM-MSC-exos, followed by histopathological evaluations using H&E, Nissl staining, and BMS scoring. RMRP was enriched in OM-MSC-exos and down-regulated in TNF-α-stimulated astrocytes. OM-MSC-exo treatment elevated RMRP expression, ECAR, glucose consumption, lactate production, LDH activity, decreased OCR in TNF-α-stimulated astrocytes, and promoted axonal regeneration. However, these effects were abolished when RMRP was down-regulated in OM-MSC-exos. Mechanistically, RMRP bound to WTAP in astrocytes, reducing WTAP expression and subsequent m6A of p53 mRNA, thereby destabilizing p53. WTAP or p53 overexpression could reverse RMRP overexpression-induced astrocyte metabolic reprogramming and DRGn axonal regeneration. In vivo assays indicated that OM-MSC-exo treatment promoted motor function, glycolysis, and axonal regeneration after SCI by transferring RMRP, with decreased WTAP and p53 expressions. OM-MSC-exo-RMRP mediates metabolic reprogramming to promote post-SCI axonal regeneration via inhibiting WTAP-mediated p53 m6A.

Keywords:  RMRP; axonal regeneration; glycolysis; m6A; olfactory mucosa mesenchymal stem cell‐derived‐exosome; spinal cord injury

DOI:  https://doi.org/10.1096/fj.202502473R
J Am Chem Soc. 2026 Jan 15.

Incorporation of Functional Proteins on Cellular Surfaces via Artificial Cell-Derived Vesicles (ACDVs) for Plasma Membrane Reprogramming.

Shuai Gong, Jingyi Qiu, Fangying Huang, Jithu Krishna, Yasin Alp, Eric Strieter, S Thayumanavan.

The complexity of cell surface proteins and their undruggable nature remain major challenges for functional modulation strategies such as small-molecule inhibition. Here, we present an artificial cell-derived vesicle (ACDV) approach that enables the direct delivery of functional proteins onto the cell surface, bypassing the need for genetic manipulation. This programmable system converts live cells into dynamic biointerfaces capable of introducing catalytic and signaling regulation, providing a broadly applicable strategy for therapeutic cell surface engineering. These ACDVs thus represent a proof-of-concept platform for the delivery of functional biologics onto plasma membranes.

DOI: https://doi.org/10.1021/jacs.5c17697