bims-engexo 2025-09-14 papers

bims-engexo

Biomed News

on Engineered exosomes

Issue of 2025–09–14
eight papers selected by
Ravindran Jaganathan, Universiti Kuala Lumpur

Labeling, isolation and characterization of cell-type-specific exosomes derived from mouse skin tissue.
The role and therapeutic potential of exosome-mediated microRNAs regulatory networks in diabetic kidney disease.
Hybridoma-inspired strategy crafts tailored multifunctional exosomes for precision therapy.
The Effects of Mesenchymal Stem Cell-Derived Exosomes on the Attenuation of Dry Eye Disease in Sjögren Syndrome Animal Model.
Exosome-mediated co-delivery of superoxide dismutase and chondroitinase ABC for multiple sclerosis therapy.
Adipose-derived mesenchymal stem cells and their derivatives in inflammatory skin diseases: a systematic review.
Stem Cell-Derived Exosomes: A Comprehensive Review of Biomedical Applications, Challenges, and Future Directions.
Novel Copper Superparticle-Based Bragg Scattering Coupling Luminescence Strategy for Detection of Ginseng Exosomal miRNA.

Nat Protoc. 2025 Sep 12.

Labeling, isolation and characterization of cell-type-specific exosomes derived from mouse skin tissue.

Anita Yadav, Anu Sharma, Mohini Moulick, Parmeshwar V Gavande, Aparajita Nandy, Yi Xuan, Chandan K Sen, Subhadip Ghatak.

Extracellular vesicles are a heterogeneous group of membrane-bound vesicles involved in cell-cell communication, formed at the plasma membrane (ectosomes) or by endocytosis (exosomes). Most exosome studies so far have focused on in vitro systems or exosomes derived from bodily fluids, while tissue-derived exosomes remain underexplored. Here we present a protocol using cell-type-specific promoter-driven reporter constructs for the targeted labeling and subsequent isolation of exosomes from specific cell types in vivo from mouse tissues. The differentiation between exosomes and ectosomes remains challenging due to limitations of current isolation techniques that are primarily based on size, density or surface markers. To address this issue, our approach leverages genetic engineering to mark exosomes specifically, enabling their precise identification and isolation from a complex biological pool of heterogenous extracellular vesicles. The isolated cell-type-specific exosomes are characterized by electron microscopy, nanoparticle tracking analysis, antibody exosome array assay and other established techniques. The labeling and isolation of exosomes spans 2-3 days and is designed to be accessible to researchers with fundamental laboratory competencies. This protocol facilitates the study of exosome-mediated cellular communication by enabling the isolation of cell-type-specific exosomes from either individual cell types or multiple cell types in combination. Most experiments within the protocol have used murine wound-edge skin tissue, but the protocol can, in principle, also be applied to other tissues to isolate exosomes, with a few modifications as required. This methodology opens new avenues for exploring the functional roles of cell-type-specific exosomes in intercellular communication.

DOI: https://doi.org/10.1038/s41596-025-01238-5
Mol Biol Rep. 2025 Sep 13. 52(1): 902

The role and therapeutic potential of exosome-mediated microRNAs regulatory networks in diabetic kidney disease.

Xiaofei Zhang, Kexin Zhang, Qiming Fan, Jiajun Sang, Chengxia Kan, Ruiyan Pan, Xiaodong Sun, Ningning Hou, Zhentao Guo.

  Diabetic kidney disease (DKD), a leading cause of end-stage renal disease, involves complex pathological mechanisms such as inflammation, fibrosis, oxidative stress, and immune dysregulation. Exosome-mediated microRNAs (miRNAs), as stable carriers of genetic material in body fluids, have emerged as crucial regulators of DKD progression by modulating intercellular communication and gene expression. This review summarizes the biogenesis and regulatory mechanisms of exosome-encapsulated miRNAs, highlighting their roles in glomerular injury, tubulointerstitial fibrosis, and immunoinflammatory responses in DKD. Specific exosomal miRNAs, including miR-21, miR-29, miR-192, and miR-155, are discussed for their contributions to renal cell injury and fibrotic progression. Moreover, exosomal miRNAs demonstrate significant potential as noninvasive biomarkers for early DKD diagnosis and disease monitoring, given their stability and tissue-specific expression profiles. Therapeutically, interventions targeting pathogenic miRNAs or delivering protective miRNAs via engineered exosomes offer promising strategies for DKD treatment. Despite current challenges related to standardization, delivery efficiency, and safety, advances in exosome engineering and nucleic acid therapeutics are expected to accelerate the clinical translation of exosomal miRNA-based precision medicine in DKD.

Keywords:  Diabetic kidney disease; Exosome; MicroRNAs; Regulatory network; Therapeutic potential

DOI:  https://doi.org/10.1007/s11033-025-11015-y
Proc Natl Acad Sci U S A. 2025 Sep 16. 122(37): e2424547122

Hybridoma-inspired strategy crafts tailored multifunctional exosomes for precision therapy.

Zhufeng Dong, Tieying Yin, Zhiqin Deng, Hang Zou, Lei Kuang, Yang Wang, Wen Shi, Mengwei Han, Siqing Zhu, Zheng Wang, Xiaoye Hu, Yazhou Z Wang.

  Engineering functional exosomes represents a cutting-edge approach in biomedicine, holding the promise to transform targeted therapy. However, challenges such as achieving consistent modification and scalability have limited their wider adoption. Herein, we introduce a universal and effective strategy for engineering multifunctional exosomes through cell fusion. The hybrid-cell-derived exosomes could combine the functional properties of both parental cells and be readily produced by passaging. This method enables customization and large-scale production of exosomes with specific functionalities, potentially advancing precision therapies across a wide array of diseases. As demonstrated in Alzheimer's disease (AD) models, exosomes derived from hybrid cells (HCs) (H/Exos) of mesenchymal stem cells (MSCs) and neutrophils efficiently targeted AD-affected areas via LFA-1/ICAM-1 and improved the cognition of AD mice. Beyond directly promoting neural repair and inhibiting inflammation, we surprisingly found that H/Exos increased microglia abundance, modulated microglia gene expression, enhanced the endocytic and lysosomal function, and promoted microglial phagocytic phenotypic differentiation to clear Aβ. This hybridoma-inspired strategy offers a versatile and practical way to engineer exosomes with desired therapeutic functions, representing a promising direction for personalized therapies.

Keywords:  Alzheimer’s disease; hybrid cells; mesenchymal stem cells; microglial differentiation; target therapeutic exosomes

DOI:  https://doi.org/10.1073/pnas.2424547122
Tissue Eng Regen Med. 2025 Sep 08.

The Effects of Mesenchymal Stem Cell-Derived Exosomes on the Attenuation of Dry Eye Disease in Sjögren Syndrome Animal Model.

Youngseo Jeon, Soojung Shin, Eun Jeong Cheon, Yongmin Kwon, Jin Uk Beak, Hyun Jung Lee, Jaesung Park, So-Hyang Chung.

   BACKGROUND: Sjögren's syndrome (SS) is a chronic autoimmune disease delineated by excessive lymphocyte infiltration to the lacrimal or salivary glands, leading to dry eye and dry mouth. Exosomes secreted from mesenchymal stem cells (MSC) are known to have anti-inflammatory and tissue regeneration abilities. This study endeavored to demonstrate the effect of MSC-derived exosomes on the clinical parameter of dry eyes and associated pathology in SS mouse model.
METHODS: Exosomes obtained from bone marrow-derived human MSC (Catholic MASTER Cells) were injected into the subconjunctival sac of 17 weeks-old NOD/LtJ female mice once and sacrificed after 7 days, or administered topically as an eyedrop every day for 14 days, then sacrificed. Clinical dry eye parameters, including tear volume and corneal staining scores, density of goblet cells in the conjunctiva, pro-inflammatory cytokine expressions of cornea and conjunctiva, and the lacrimal glands were evaluated. Infiltration of inflammatory foci, and expression of B and T cells in the lacrimal glands were examined.
RESULTS: Tear volume, corneal stain scores and density of goblet cells in conjunctiva were improved in the exosome-treated groups compared to the control group. Pro-inflammatory cytokine expressions were also reduced in the cornea and conjunctiva of the exosome-treated group. In the lacrimal glands of the exosome-treated mice, inflammatory foci infiltration and B cell marker expressions were significantly decreased.
CONCLUSIONS: Thus, this study demonstrated the amelioration of dry eyes with the administration of exosomes in SS animal model, suggesting promising therapeutic potential of MSC-derived exosomes in SS dry eyes.

Keywords:  Dry eye; MSCs-derived exosome; Sjögren’s syndrome

DOI:  https://doi.org/10.1007/s13770-025-00755-4
Int J Biol Macromol. 2025 Sep 04. pii: S0141-8130(25)07995-4. [Epub ahead of print]327(Pt 1): 147438

Exosome-mediated co-delivery of superoxide dismutase and chondroitinase ABC for multiple sclerosis therapy.

Xinxin Shao, Xinxin Feng, Jinran Feng, Tianyuan Qiu, Shengcai Yang, Quanshun Li.

  Multiple sclerosis is an autoimmune demyelinating disease, and its effective treatment is a great challenge. As a typical animal model for studying multiple sclerosis, experimental autoimmune encephalomyelitis (EAE) is characterized by inflammation, demyelination, gliosis and axonal loss. Thus, simultaneous regulation of neuroinflammation and remyelination may be a useful strategy against EAE. Herein, superoxide dismutase (SOD) and chondroitinase ABC (ChABC) were co-encapsulated in exosomes to obtain SOD and ChABC-loaded exosomes (SOD/ChABC@EXO) to investigate whether the combination of therapeutic enzymes was effective in the treatment of EAE. The SOD/ChABC@EXO was found to possess high SOD and ChABC activities, which could scavenge intracellular reactive oxygen species and inhibit the apoptosis of lipopolysaccharide-activated BV2 cells. Meanwhile, intranasal administration of SOD/ChABC@EXO could achieve the high accumulation of enzyme molecules in spinal cord and brain, and manifest the modulation of neuroinflammation and remyelination in EAE mice model. Overall, the exosome-mediated intranasal co-delivery of SOD and ChABC provides a potential strategy to treat multiple sclerosis.

Keywords:  Chondroitinase ABC; Exosome; Superoxide dismutase

DOI:  https://doi.org/10.1016/j.ijbiomac.2025.147438
Front Immunol. 2025 ;16 1617157

Adipose-derived mesenchymal stem cells and their derivatives in inflammatory skin diseases: a systematic review.

Mateusz Matwiejuk, Agnieszka Mikłosz, Hanna Myśliwiec, Adrian Chabowski, Iwona Flisiak.

  Adipose-derived mesenchymal stem cells (ADMSCs) offer a multifaceted approach to treating immune-mediated skin diseases by modulating the immune system and promoting tissue regeneration. Specifically, their ability to differentiate into multiple cell types such as keratinocytes and fibroblasts, modulate immune responses, and release growth factors and cytokines underscores their potential in treating a wide range of immune-related skin conditions. ADMSCs significantly reduced various aspects of psoriasis, including scaling, thickness, and erythema. Moreover, cell-free therapy has even better therapeutic potential. It has been shown that ADMSC-derived exosomes can effectively alleviate pathological symptoms of atopic dermatitis, including clinical score, serum IgE levels, eosinophil amount, and infiltration of immune cells in skin lesions. This systematic review summarizes the most relevant preclinical and clinical studies on the therapeutic use of ADMSCs and their small extracellular vesicles in the treatment of common skin diseases like psoriasis, atopic dermatitis, localized scleroderma and acne vulgaris.

Keywords:  ADMSCs; acne vulgaris; atopic dermatitis; exosomes; localized scleroderma; psoriasis; skin diseases; small extracellular vesicles

DOI:  https://doi.org/10.3389/fimmu.2025.1617157
Int J Nanomedicine. 2025 ;20 10857-10905

Stem Cell-Derived Exosomes: A Comprehensive Review of Biomedical Applications, Challenges, and Future Directions.

Jingyi Zhang, Xingzhao Tian, Yi Li, Chunyan Fang, Fang Yang, Liang Dong, Yifeng Shen, Shiyun Pu, Junjun Li, Degui Chang, Lanjie Lei, Xujun Yu.

  Stem cell-derived exosomes (SC-Exos) represent an innovative therapeutic breakthrough that circumvents key limitations of direct stem cell transplantation, demonstrating significant therapeutic potential while offering distinct advantages including reduced ethical controversies, decreased immunogenicity responses, and minimized tumorigenicity risks. This review provides a systematic analysis of SC-Exos research, encompassing diverse aspects from fundamental biological mechanisms and isolation and characterization techniques to advanced engineering strategies and therapeutic applications. The review elucidates the biological foundations of exosomes, analyzes different SC-Exos types and their unique characteristics, and explores multiple functional optimization strategies to enhance SC-Exos performance. Comprehensive biomedical engineering applications of SC-Exos across diverse therapeutic domains are presented, covering tissue engineering, advanced drug delivery systems, and treatments for cardiovascular, neurological, oncological, immunological, inflammatory, reproductive, musculoskeletal, and dermatological diseases, as well as other emerging applications. Clinical translation status is evaluated through analysis of current trials, revealing favorable safety profiles and promising preliminary efficacy of SC-Exos across multiple therapeutic domains. Nevertheless, significant challenges remain in standardization of isolation and purification techniques, quality control measures, therapeutic heterogeneity, scalable production capabilities, and comprehensive biosafety evaluation protocols. Future research priorities include establishing unified isolation and purification standards, developing comprehensive functional evaluation systems, optimizing administration routes and dosing regimens, and conducting large-scale multicenter clinical trials. This review provides systematic guidance for advancing effective SC-Exos-based therapeutic solutions, ultimately facilitating their clinical translation and expanding applications across biomedical challenges.

Keywords:  biomedical applications; biomedical engineering; clinical translation; extracellular vesicles; nanomedicine; stem cell-derived exosomes

DOI:  https://doi.org/10.2147/IJN.S527137
Anal Chem. 2025 Sep 07.

Novel Copper Superparticle-Based Bragg Scattering Coupling Luminescence Strategy for Detection of Ginseng Exosomal miRNA.

Jianhui Lyu, Peilin Wang, Ning Liu, Wenyan Li, Qiang Ma.

Ginseng exosomes are a kind of promising extracellular vesicle containing unique bioactive components. However, the investigation on ginseng-derived exosomes is still in the initial stage. This study developed a photonic crystal-based Bragg scattering coupling electrochemiluminescence (BSC-ECL) biosensor for detection of miRNA396a-3p in exosome-like nanoparticles (GENs) and ginseng exosomes (Gexos). First, copper nanoclusters were engineered into Cu superparticles with π-π stacking of 2,6-dimethylbenzenethiol ligands via a ligand-mediated self-assembly strategy. The prepared Cu superparticles with significantly enhanced luminescence intensity and stability can be used as a nanoprobe. Furthermore, the Bragg scattering law was utilized to modulate the ECL intensity of the Cu superparticles. Due to the highly periodic structure of MIL-96-based photonic crystals, multiple scattering pathways in photonic crystals greatly increased the effective photon flux of Cu superparticles, thus creating a positive feedback loop between photon absorption and emission. Therefore, this cascade amplification mechanism ultimately led to significant BSC-ECL enhancement. The BSC-ECL provided a new quantitative analysis method for key miRNA detection in plant extracellular vesicles, which revealed distinct miRNA concentrations in GENs and Gexos. The method also demonstrated considerable potential in areas such as ginseng quality control, product development, and bioanalysis applications.

DOI: https://doi.org/10.1021/acs.analchem.5c03381