bims-engexo 2025-06-01 papers

bims-engexo

Biomed News

on Engineered exosomes

Issue of 2025–06–01
fourteen papers selected by
Ravindran Jaganathan, Universiti Kuala Lumpur

Engineered exosomes: a promising drug delivery platform with therapeutic potential.
Immunoinformatics Analysis of Potent Therapeutic Formulations for the Development of HIV-1 Nefmut-Carrying Engineered Exosomes.
Screening scaffold proteins for improved functional delivery of luminal proteins using engineered extracellular vesicles.
Natural saponins and macrophage polarization: Mechanistic insights and therapeutic perspectives in disease management.
Genetically engineered extracellular vesicles expressing decoy protein TACI provide a therapeutic effect in systemic lupus erythematosus mouse model.
The supportive role of stem cells-derived exosomes in the embryo implantation process by regulating oxidative stress.
Macrophage-Derived Exosomal MALAT1 Regulates Autophagy through miR-204-5p/ATG7 Axis in H9C2 Cardiomyocytes and Diabetic Rat Heart.
Endometriosis-derived exosomes encapsulated miR-196a-5p mediate macrophage polarization through regulation of the Hippo pathway.
Efficient isolation and characterization of Serum-Derived Exosomes: evaluating ultracentrifugation and Total Exosome Isolation Reagent based precipitation.
Exosomes derived from fibroblasts enhance skin wound angiogenesis by regulating HIF-1α/VEGF/VEGFR pathway.
Synergistic strategies in tissue engineering: The role of exosomes and decellularized extracellular matrix hydrogels.
Novel strategies in liquid biopsy.
Adipose Mesenchymal Stem Cell-Derived Exosomes Versus Platelet-Rich Plasma Treatment for Photoaged Facial Skin: An Investigator-Blinded, Split-Face, Non-Inferiority Trial.
Glutamatergic Regulation of miRNA-Containing Intraluminal Vesicle Trafficking and Extracellular Vesicle Secretion From Cortical Neurons.

Front Mol Biosci. 2025 ;12 1583992

Engineered exosomes: a promising drug delivery platform with therapeutic potential.

Genevieve Schwarz, Xuechen Ren, Wen Xie, Haitao Guo, Yong Jiang, Jinyu Zhang.

  Exosomes, small membranous vesicles naturally secreted by living cells, have garnered attention for their role in intercellular communication and therapeutic potential. Their low immunogenicity, high biocompatibility, and efficient biological barrier penetration make them promising drug delivery vehicles. This review spans research developments from 2010 to 2025, covering the engineering of exosomes to optimize cargo loading and targeting specificity. We discuss their applications in treating cardiovascular diseases, liver fibrosis, immune diseases, and neurological diseases, alongside ongoing clinical trials and industry progress. Future challenges include scalability, standardization, and minimizing off-target effects. We propose strategies to address these hurdles, such as bioengineering techniques and improved isolation methods. By synthesizing current knowledge and outlining future directions, this review aims to guide researchers toward harnessing exosomes for disease treatment.

Keywords:  Exosomes; and nervous disorders; cardiovascular diseases; immune diseases; liver fibrosis

DOI:  https://doi.org/10.3389/fmolb.2025.1583992
Curr HIV Res. 2025 May 21.

Immunoinformatics Analysis of Potent Therapeutic Formulations for the Development of HIV-1 Nefmut-Carrying Engineered Exosomes.

Parisa Moradi Pordanjani, Azam Bolhassani, Fatemeh Heidarnejad, Elnaz Agi.

   BACKGROUND: The concept of designer exosomes involves developing engineered ex-osomes to overcome the limitations of natural exosomes in targeted drug delivery and vaccine development.
METHODS: In this study, the multiepitope constructs were designed based on immunogenic regions of mutant Nef protein of Human Immunodeficiency Virus-1 (HIV-1 Nefmut) that were prone to high Post-Translational Modifications (PTMs), such as palmitoylation and myristoylation. These constructs with high scores in PTMs were selected for interactions with molecules involved in exosome biogenesis, anchoring of a protein in membranes, and enzymes involved in PTMs (e.g., the mutant enzyme ZDHHC21 p.T209S). Moreover, the selected multiepitope construct with the highest PTM score and stable linkage with these molecules was fused to the first exon of the HIV-1 Tat protein as an antigen candidate, and to GFP as a tracking tool for evaluating their effects on the PTM scores and affinity binding with various molecules.
RESULTS: Our data demonstrated that the multiepitope construct No.13 had better scores for incor-poration into exosomes compared to the whole sequences of Nefmut and wild-type Nef protein (Nefwt). Furthermore, the linkage of Tat protein to construct No. 13 did not hinder its loading in exosomes compared to GFP, suggesting the use of this construct in vaccine development.
CONCLUSION: The multiepitope construct No.13 harboring potent Nef mut epitopes can be applied for linkage with other viral antigens, enhancing their delivery into exosomes for therapeutic ap-plications.

Keywords:  Computational study.; Exosome; HIV-1 Nefwt; Nefmut; Palmitoylation and myristoylation; Post-translational modification

DOI:  https://doi.org/10.2174/011570162X361821250512115612
J Control Release. 2025 May 26. pii: S0168-3659(25)00502-4. [Epub ahead of print]384 113882

Screening scaffold proteins for improved functional delivery of luminal proteins using engineered extracellular vesicles.

Zheyu Niu, Houze Zhou, Wenyi Zheng, Oliver G Hayes, Vicky W Q Hou, André Görgens, Samantha Roudi, Guannan Zhou, Rim Jawad Wiklander, Taras Sych, Erdinc Sezgin, Joel Z Nordin, Ying Zhao, Xiuming Liang, Samir E L Andaloussi.

  The potential for engineered extracellular vesicles (EVs) to efficiently deliver biotherapeutics is still largely untapped. One of the key structures in determining cargo loading and subsequent functional delivery efficiency of engineered EVs is the sorting protein (scaffold). To determine the role of scaffold protein identity, a functional screen of scaffold proteins for efficient cargo delivery is required. Here, we applied the VEDIC (VSV-G plus EV-sorting Domain-Intein-Cargo) system, previously developed by our group, for the functional screen of 55 different scaffold proteins. Three tetraspanins (TSPAN2, TSPAN4 and TSPAN9) were identified that demonstrate enhanced intracellular delivery of cargo when compared to traditionally used CD63. We further explored the in vivo and ex vivo protein delivery performance of the best performing engineered EVs (TSPAN2) using melanoma xenografts and isolated primary cells from Cre-LoxP R26-LSL-tdTomato reporter mice, respectively. Finally, we report successful treatment of LPS-induced systemic inflammation by delivering a super-repressor inhibitor of NF-ĸB using TSPAN2 engineered EVs. This work highlights the importance of screening critical EV engineering elements, such as the scaffold protein, to modulate EV properties.

Keywords:  Extracellular vesicles; Intracellular delivery; Scaffold protein; TSPAN2

DOI:  https://doi.org/10.1016/j.jconrel.2025.113882
Front Pharmacol. 2025 ;16 1584035

Natural saponins and macrophage polarization: Mechanistic insights and therapeutic perspectives in disease management.

Beibei Xiong, Huan Wang, Yi-Xuan Song, Wen-Ying Lan, Jiangtao Li, Fang Wang.

  Macrophage polarization plays a pivotal role in immune homeostasis and disease progression across inflammatory, neoplastic, and metabolic disorders. Saponins, which are natural compounds with steroidal/triterpenoid structures, demonstrate therapeutic potential through immunomodulatory, anti-inflammatory, and anti-tumor activities. This study aims to highlight the potential of key saponins-such as ginsenosides, astragaloside IV, dioscin, platycodin D, pulsatilla saponins, and panax notoginseng saponins-in modulating macrophage polarization and enhancing conventional therapies, particularly in oncology. We conducted structured searches in PubMed, Google Scholar, and SciFinder (2013-2024) using controlled vocabulary, including "saponins," "macrophage polarization," and "therapeutic effects." Our findings demonstrate that saponins significantly modulate immune responses and improve treatment efficacy. However, clinical translation is hindered by challenges such as poor bioavailability and safety concerns, which limit systemic exposure and therapeutic utility. To overcome these barriers, innovative delivery strategies, including nanoemulsions and engineered exosomes, are essential for enhancing pharmacokinetics and therapeutic index. Future research should prioritize elucidating the molecular mechanisms underlying saponin-mediated macrophage polarization, identifying novel therapeutic targets, and optimizing drug formulations. Addressing these challenges will enable the restoration of immune balance and more effective management of diverse diseases.

Keywords:  bioavailability; macrophage polarization; molecular mechanism; natural products; pharmacokinetics; saponin

DOI:  https://doi.org/10.3389/fphar.2025.1584035
J Control Release. 2025 May 25. pii: S0168-3659(25)00506-1. [Epub ahead of print] 113886

Genetically engineered extracellular vesicles expressing decoy protein TACI provide a therapeutic effect in systemic lupus erythematosus mouse model.

Menghua Cai, Feng Tian, Jingyi Han, Liang Wang, Shikai Hu, Peng Dong, Wenhua Qiao, Han Zhang, Yue Wang, Hui Chen, Wei He, Jianmin Zhang.

  The suppression of B-cell activation and autoantibody production through immunotherapy has garnered substantial interest in advancing systemic lupus erythematosus (SLE) treatments. Although SLE patients do benefit from current therapies, no efficient therapeutic approaches are available to a substantial number of patients. In this study, we developed extracellular vesicles to express a fusion protein of the transmembrane activator and cyclophilin ligand interaction molecule (TACI). We performed a comprehensive functional evaluation, including in vitro binding assays and therapeutic efficacy assessments in a murine SLE model. Our findings demonstrate that the engineered extracellular vesicles stably express the TACI receptor, effectively bind the cytokine BLyS and inhibit the BCMA-NF-κB signaling pathway in vitro. In vivo, TACI-engineered small extracellular vesicles significantly attenuated SLE severity and reduced inflammatory kidney damage in SLE mice by blocking BLyS/APRIL signaling. Collectively, these findings highlight the therapeutic potential of TACI-engineered small extracellular vesicles as a novel approach to suppress autoimmunity, prolong survival, and ameliorate lupus nephritis in MRL/lpr mice.

Keywords:  B cells; Extracellular vesicles; Lupus nephritis; SLE; TACI

DOI:  https://doi.org/10.1016/j.jconrel.2025.113886
Biomed Pharmacother. 2025 May 22. pii: S0753-3322(25)00365-8. [Epub ahead of print]188 118171

The supportive role of stem cells-derived exosomes in the embryo implantation process by regulating oxidative stress.

Rezvan Asgari, Sahar Rashidi, Bijan Soleymani, Mitra Bakhtiari, Pantea Mohammadi, Reza Yarani, Kamran Mansouri.

  Oxidative stress can affect many aspects of the reproduction process. The embryo implantation process is also one of the critical steps in establishing a successful pregnancy, and several factors, including oxidative stress, can impact the process. Oxidative stress is a state of imbalance between pro-oxidant molecules such as reactive oxygen species (ROS) and antioxidant defenses. Excessive levels of ROS cause damage to the cellular macromolecules such as nucleic acids, proteins, and lipids, resulting in cell dysfunction and pathological conditions. Recently, studies have displayed the therapeutic and antioxidant properties of exosomes derived from stem cells. Exosomes are one type of extracellular vesicles (EVs) secreted by almost all cells and contain different biomolecules. The unique properties of exosomes, like regulation of biological processes, transportation of biomolecules, stability, and biodegradability, can make exosomes a promising therapeutic option in reproductive disorders and diseases. Exosomes also can significantly improve the curative effect of oxidative stress-related pathogenesis. Accordingly, this review aims to provide a novel overview of how exosomes derived from stem cells can regulate oxidative stress and support the process of embryo implantation, hoping to pave the way to clinical applications and future research in this field.

Keywords:  Exosome; Extracellular vesicles; Implantation; Oxidative stress; ROS; Stem cell

DOI:  https://doi.org/10.1016/j.biopha.2025.118171
Acta Cardiol Sin. 2025 May;41(3): 346-360

Macrophage-Derived Exosomal MALAT1 Regulates Autophagy through miR-204-5p/ATG7 Axis in H9C2 Cardiomyocytes and Diabetic Rat Heart.

Kou-Gi Shyu, Bao-Wei Wang, Chun-Ming Pan, Wei-Jen Fang.

   Background: Autophagy activity is tightly associated with cardiovascular disease development and progression. The effect of exosomal metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) derived from macrophages treated with high levels of glucose on autophagy in cardiomyocytes and diabetic hearts is not known. We investigated the effect of autophagy and its regulatory mechanisms on H9C2 cardiomyocytes and diabetic hearts by macrophage-derived exosomal MALAT1.
Methods: Mouse macrophages and rat H9C2 cardiomyocytes were cultured, and exosomes were extracted from the culture media. A diabetic model was established through the injection of streptozotocin into adult male Wistar rats. Reverse transcription real-time quantitative polymerase chain reaction, Western blotting, immunohistochemical staining, autophagosome and/or autolysosome fluorescent cell staining, and luciferase activity assays were performed.
Results: High glucose significantly enhanced exosomal MALAT1 expression in cultured H9C2 cells and macrophages. Macrophage-derived exosomes significantly increased autophagy-related 7 (ATG7) and decreased miR-204-5p expressions. Silencing MALAT1 by MALAT1 small interference RNA and the overexpression of wild-type miR-204-5p significantly decreased the ATG7 expression induced by macrophage-derived exosomes. MiR-204-5p significantly decreased MALAT1 and ATG7 luciferase activity in cultured H9C2 cells treated with macrophage-derived exosomes. Streptozotocin-induced diabetes mellitus and macrophage-derived exosomes significantly enhanced MALAT1 expression to inhibit miR204-5p expression in the rat hearts. Macrophage-derived exosomes significantly enhanced ATG7 expression in the streptozotocin-induced diabetic hearts.
Conclusions: In conclusion, we discovered that exosomal MALAT1 derived from macrophages after high glucose treatment could sequester miR-204-5p, leading to the upregulation of ATG7 expression, and this was linked to the regulation of autophagy in H9C2 cardiomyocytes and streptozotocin-induced diabetic hearts.

Keywords:  ATG7; Autophagy; Cardiomyocytes; Exosome; MALAT1; Macrophage

DOI:  https://doi.org/10.6515/ACS.202505_41(3).20250224D
J Cell Commun Signal. 2025 Jun;19(2): e70020

Endometriosis-derived exosomes encapsulated miR-196a-5p mediate macrophage polarization through regulation of the Hippo pathway.

Bin Lu, Qixiang Huang, Yanyu Zhong.

  Endometriosis (EMs) is a disease that adversely affects women's health. Immune imbalance is an important factor contributing to EMs, and exosomes (Exo) play an important role in immunomodulation. The purpose of this study was to investigate the effect of exosomes derived from the blood of patients with EMs on macrophage polarization and elucidate the underlying mechanisms. Exosomes were isolated from the serum of healthy controls (control exosomes) and patients with EMs (EMs exosomes). Macrophage polarization levels were detected using flow cytometry (FCM), RT-qPCR, and Western blot. Subsequently, we used RNA sequencing to analyze differential microRNAs (miRNA) and associated pathways. Electroporation techniques were used to modify the exosomes. The associated pathways were analyzed by Western blot. Finally, 12Z cells were co-cultured with macrophages of different polarizations, and the viability and metastasis of 12Z cells were calculated by cell counting kit-8 (CCK-8), scratch, and Transwell. EMs exosomes induced M2-type polarization in macrophages. RNA sequencing results showed that miR-196a-5p was dramatically decreased in EMs exosomes, whereas overexpression of miR-196a-5p in EMs exosomes could inhibit the M2-type polarization of macrophages and activate the Hippo pathway. In addition, M2-type macrophages promoted 12Z cell proliferation and metastasis. These findings suggest that serum-derived exosomes encapsulating miR-196a-5p alleviate endometriosis by promoting M1-type macrophage polarization via Hippo pathway activation.

Keywords:  Hippo pathway; endometriosis; exosome; macrophage; miR‐196a‐5p

DOI:  https://doi.org/10.1002/ccs3.70020
Ultrastruct Pathol. 2025 May 25. 1-14

Efficient isolation and characterization of Serum-Derived Exosomes: evaluating ultracentrifugation and Total Exosome Isolation Reagent based precipitation.

Ranjana Bharti, Munish Kumar, Veena Devi, Asha Rao, Ashish Aggarwal, Tulika Gupta.

  Exosomes are extracellular vesicles that carry biomolecular cargos such as proteins, lipids, RNA, and DNA. These molecules play crucial roles in cell-to-cell communication and are involved in various physiological and pathological processes. Due to their potential as biomarkers for disease diagnosis and prognosis, research has increasingly focused on developing more efficient methods for their isolation and characterization. In this study, blood samples were collected from 30 participants, and serum was subsequently isolated. Serum-derived exosomes (SDEs) were extracted using ultracentrifugation (UC) as well as the Total Exosome Isolation Reagent. Modifications to the UC method were implemented to improve yield and purity, and a detailed description of the method is also provided. The exosomes were characterized by Transmission Electron Microscopy (TEM), Scanning Electron Microscopy (SEM), Dynamic Light Scattering (DLS), and Western Blotting (WB) to evaluate their size, morphology, and protein content. The exosome yields from both isolation methods were evaluated using the BCA assay. Protein estimation suggested that the Total Exosome Isolation Reagent produced exosome concentrations that were 10-fold higher compared to those obtained through ultracentrifugation. Morphological analysis showed that exosomes exhibited circular, spherical, and irregular shapes, with diameters ranging from 30 to 200 nm. Western Blotting confirmed the presence of exosomal markers (TSG101, ALIX, LAMP2, and CD63) in the SDEs. In conclusion, both ultracentrifugation and the Total Exosome Isolation Reagent effectively isolate SDEs. Thus, although both methods are viable, modified ultracentrifugation is the preferred choice for applications due to its cost-effectiveness and suitability for achieving pure protein yields.

Keywords:  Exosome characterization; exosome isolation; extracellular vesicles (EVs); serum-derived exosomes (SDEs); ultracentrifugation

DOI:  https://doi.org/10.1080/01913123.2025.2507698
Burns Trauma. 2025 ;13 tkae071

Exosomes derived from fibroblasts enhance skin wound angiogenesis by regulating HIF-1α/VEGF/VEGFR pathway.

Yunxia Chen, Wenjing Yin, Zhihui Liu, Guang Lu, Xiaorong Zhang, Jiacai Yang, Yong Huang, Xiaohong Hu, Cheng Chen, Ruoyu Shang, Wengang Hu, Jue Wang, Han-Ming Shen, Jun Hu, Gaoxing Luo, Weifeng He.

   Background: Angiogenesis is vital for tissue repair but insufficient in chronic wounds due to paradoxical growth factor overexpression yet reduced neovascularization. Therapeutics physiologically promoting revascularization remain lacking. This study aims to investigate the molecular mechanisms underlying fibroblast-derived exosome-mediated angiogenesis during wound repair.
Methods: To assess the effects of fibroblasts derived exosomes on wound healing and angiogenesis, a full-thickness mouse skin injury model was established, followed by pharmacological inhibition of exosome secretion. The number and state of blood vessels in wounds were assessed by immunofluorescence, immunohistochemistry, hematoxylin-eosin staining, and laser Doppler imaging system. The high-throughput miRNA sequencing was carried out to detect the miRNA profiles of fibroblast-derived exosomes. The roles of candidate miRNAs, their target genes, and relevant pathways were predicted by bioinformatic online software. The knockdown and overexpression of candidate miRNAs, co-culture system, matrigel assay, pharmacological blockade, cell migration, EdU incorporation assay, and cell apoptosis were employed to investigate their contribution to angiogenesis mediated by fibroblast-derived exosomes. The expression of vascular endothelial growth factor A (VEGFA), vascular endothelial growth factor receptor 2 (VEGFR2), hypoxia-inducible factor 1α (HIF-1α), von Hippel-Lindau (VHL), and proline hydroxylases 2 was detected by western blot, co-immunoprecipitation, immunofluorescence, real-time quantitative polymerase chain reaction, flow cytometry, and immunohistochemistry. Furthermore, a full-thickness mouse skin injury model based on type I diabetes mellitus induced by streptozotocin was established for estimating the effect of fibroblast-derived exosomes on chronic wound healing.
Results: Pharmacological inhibition of exosome biogenesis markedly reduces neovascularization and delays murine cutaneous wound closure. Topical administration of fibroblast-secreted exosomes rescues these defects. Mechanistically, exosomal microRNA-24-3p suppresses VHL E3 ubiquitin ligase levels in endothelial cells to stabilize hypoxia-inducible factor-1α and heighten vascular endothelial growth factor signaling. MicroRNA-24-3p-deficient exosomes exhibit attenuated pro-angiogenic effects. Strikingly, topical application of exosomes derived from fibroblasts onto chronic wounds in diabetic mice improves neovascularization and healing dynamics.
Conclusions: Overall, we demonstrate central roles for exosomal miR-24-3p in stimulating endothelial HIF-VEGF signaling by inhibiting VHL-mediated degradation. The findings establish fibroblast-derived exosomes as promising acellular therapeutic candidates to treat vascular insufficiency underlying recalcitrant wounds.

Keywords:  Angiogenesis; Exosomes; Fibroblasts; MicroRNA-24-3p; Wound healing

DOI:  https://doi.org/10.1093/burnst/tkae071
Biomed Pharmacother. 2025 May 24. pii: S0753-3322(25)00394-4. [Epub ahead of print]188 118200

Synergistic strategies in tissue engineering: The role of exosomes and decellularized extracellular matrix hydrogels.

Fatemeh Soltanmohammadi, Adel Mahmoudi Gharehbaba, Yousef Javadzadeh.

  Tissue engineering aims to mimic the natural microenvironment of biological structures by utilizing the distinctive characteristics of extracellular matrix (ECM) scaffolds. The combination of decellularized extracellular matrix hydrogels (dECMHs) with exosomes (EXs) represents an innovative therapeutic approach for tissue regeneration. These dECMHs, sourced from diverse tissues, provide biocompatible scaffolds that conform to irregular defect geometries, thereby addressing the limitations of conventional ECM scaffolds. EXs, which are nanovesicles secreted by virtually all cells, play crucial role in cell communication and tissue regeneration. However, their short half-life presents challenges for systemic administration. The incorporation of EXs into dECMHs enables localized and prolonged release, thereby enhancing their therapeutic merits. This review thoroughly explains the techniques for decellularization, the characteristics of dECM, as well as the preparation and applications of dECMHs in tissue engineering. It also explores the synergistic effects of EX-dECMH systems on cellular activities essential for tissue repair, including proliferation, differentiation, and neovascularization. The mechanisms of EX release from dECMHs and their applications in the regeneration of skin, intervertebral disc, cartilage, and nerve tissues are elucidated, highlighting the considerable potential of this integrated strategy to improve tissue engineering techniques. Furthermore, the synergistic effect of EX-dECMH systems in tissue healing is investigated. Finally, the limitations associated with the clinical application of EX, dECM, and dECMH as well as the future prospect are included.

Keywords:  Decellularized extracellular matrix; Decellularized extracellular matrix hydrogel; Exosome; Hydrogel; Tissue engineering

DOI:  https://doi.org/10.1016/j.biopha.2025.118200
Clin Chim Acta. 2025 May 23. pii: S0009-8981(25)00264-5. [Epub ahead of print]576 120385

Novel strategies in liquid biopsy.

Qinyue Guo, Liang Shan, Jizhuang Luo, Yiman Huang, Yunxia Bao, Xianzhao Wang, Lifang Ma, Gang Wang.

  Cancer, a leading global cause of death, involves complex processes and multiple components. Due to the lack of effective and accurate early diagnostic methods, many patients are diagnosed with advanced cancer. Traditional tissue biopsy, while common, may increase the risk of metastasis. In contrast, liquid biopsy technology utilizes bodily fluids such as blood, urine, and saliva to analyze tumor-associated information, including circulating tumor DNA (ctDNA), circulating tumor cells (CTCs), exosomes, and various molecular markers. This technology has undergone rapid advancements, enabling its routine clinical use in cancer patients and broadening research horizons. ctDNA and CTCs can be isolated and analyzed from blood sample, providing valuable insights for therapeutic choices. However, technical and clinical challenges remain, such as the low proportion of ctDNA in circulating free DNA, the short half-life of ctDNA in blood, and the low concentration and heterogeneity of CTCs. Exosomes, abundant and stable vesicles released by most cells, carry bioactive molecules and play a pivotal role in intercellular communication, tumorigenesis, and progression. They offer advantages over CTCs and ctDNA but also present challenges in isolation, detection, and specificity. This review summarizes recent technologies for detecting ctDNA, CTCs, and exosomes in liquid biopsies, including nanotechnology, sensor technology, spectroscopy, microfluidic technology, and aptamers. It highlights their clinical applications and future development directions, elucidating their promising prospects in diagnosing cancer patients, monitoring disease progression, and predicting prognosis.

Keywords:  Circulating tumor DNA; Circulating tumor cells; Exosomes; Liquid biopsy; Methodology

DOI:  https://doi.org/10.1016/j.cca.2025.120385
J Cosmet Dermatol. 2025 May;24(5): e70208

Adipose Mesenchymal Stem Cell-Derived Exosomes Versus Platelet-Rich Plasma Treatment for Photoaged Facial Skin: An Investigator-Blinded, Split-Face, Non-Inferiority Trial.

Blanca Estupiñan, Karen Ly, David J Goldberg.

   BACKGROUND: Exosomes, an emerging treatment of interest to aesthetic dermatology, have therapeutic applications in skin rejuvenation, alopecia, atopic dermatitis, acne scarring, and wound healing. Platelet-rich plasma has been widely utilized for the same indications, among others. Currently, there are no trials comparing the two regenerative modalities in aesthetic dermatology.
AIMS: To compare the efficacy and safety of adipose mesenchymal stem cell-derived (ASC) exosomes versus platelet-rich plasma for photoaged facial skin.
METHODS: An investigator-blinded, split-face trial was conducted. Participants with mild to moderate photoaging underwent three radiofrequency microneedling treatments with PRP and topical exosomes each applied to one half of the face.
RESULTS: Both exosomes and PRP equally improved wrinkling, dyschromia, erythema, texture, and overall skin appearance. Histological analysis confirmed increased collagen I and glycosaminoglycans, without significant differences between treatment arms.
CONCLUSION: ASC exosomes are a promising PRP-alternative that may be attractive to needle-averse patients and can hasten the office visit duration, as phlebotomy and centrifugation are not required.

Keywords:  exosomes; platelet‐rich plasma; radiofrequency microneedling

DOI:  https://doi.org/10.1111/jocd.70208
J Extracell Vesicles. 2025 Jun;14(6): e70100

Glutamatergic Regulation of miRNA-Containing Intraluminal Vesicle Trafficking and Extracellular Vesicle Secretion From Cortical Neurons.

Marcela Bertolio, Qiyi Li, Francesca E Mowry, Kathryn E Reynolds, Rashed Alananzeh, Haichao Wei, Kyoeun Keum, Rachel Jarvis, Jiaqian Wu, Yongjie Yang.

  Neuronal extracellular vesicles (microvesicles and exosomes) are emerging secreted vesicular signals that play important roles in the CNS. Currently, little is known about how glutamatergic signalling affects the subcellular localisation of exosome precursor intraluminal vesicles (ILVs), microRNA (miR) packaging into ILVs and in vivo spreading of neuronal EVs. By selectively labelling ILVs and exosomes (but not plasma membrane-derived MVs) with GFP-tagged human CD63 (hCD63-GFP) in cortical neurons, we found that glutamate stimulation significantly redistributes subcellular localisation of hCD63-GFP+ ILVs, especially decreasing its co-localisation with multi-vesicular body (MVB) marker Rab7 while substantially promoting EV secretion. Interestingly, glutamate stimulation only modestly alters EV miR profiles based on small RNA sequencing. Subsequent in vivo cortical neuronal DREADD activation leads to significantly more widespread hCD63-GFP+ area in hCD63-GFPf/+ mice, consistently supporting the stimulatory effect of glutamatergic activation on neuronal EV secretion and spreading. Moreover, in situ localisation of hCD63-GFP+ ILVs and hCD63-GFP+ secreted exosomes from specialised HB9+ and DAT+ neurons were also illustrated in the CNS. Taken together, our results demonstrated that glutamate activity stimulates neuronal exosome secretion and spreading in vitro and in vivo, but only modestly affects miR cargo packaging in neuronal exosomes.

Keywords:  CD63; extracellular vesicles; glutamate stimulation; intraluminal vesicles (ILVs); microRNA

DOI:  https://doi.org/10.1002/jev2.70100