bims-engexo 2025-10-05 papers

bims-engexo

Biomed News

on Engineered exosomes

Issue of 2025–10–05
thirteen papers selected by
Ravindran Jaganathan, Universiti Kuala Lumpur

Engineered exosomes: a promising approach for overcoming challenges in pancreatic cancer therapy.
Engineered exosomes with KrasG12D specific siRNA in pancreatic cancer: a phase I study with immunological correlates.
Precision Medicine: Design of Immune Inert Exosomes for Targeted Gene Delivery.
Modulation of ASC-derived extracellular vesicles containing cargo that specifically enhances wound healing.
M2 polarization of macrophages: Manipulation of spinal cord injury repair.
Silencing the fibronectin gene (FN1) improves NaCl-induced cardiac fibrosis via ferritinophagy-mediated ferroptosis in a nuclear receptor coactivator 4 (NCOA4)-dependent manner.
How Advanced Are Exosomes as Cell-Free Therapeutics for Spinal Cord Injury?
Mesenchymal stromal cell secretome in scaffold-based drug delivery: Advances, applications, and future directions.
The utilization of exosomes in hydrogels: a bibliometric analysis of publications from 2015 to May 2025.
Chemiluminescent optical fiber biosensing platform with tyramide signal amplification for ultrasensitive detection of tumor-derived exosomes.
Bone marrow mesenchymal stem cell-derived exosomal lactate dehydrogenase A promotes tendon-bone healing via histone lactylation-mediated cartilage regeneration.
Enzyme-free quantification of breast cancer-derived exosomes via cubic DNA nanostructure-enhanced hybridization chain reaction.
Exosomes derived from mesenchymal stem cells repair ovarian function by suppressing NLRP3-mediated pyroptosis in cyclophosphamide-induced premature ovarian failure.

J Nanobiotechnology. 2025 Sep 29. 23(1): 619

Engineered exosomes: a promising approach for overcoming challenges in pancreatic cancer therapy.

Mo Sha, Yang Gao, Xu Yin, Xueyao Li, Caiqi Liu, Shuang Li.

  Pancreatic cancer (PC) is among the deadliest types of cancer, with very low chances of survival. It is often asymptomatic in the early stage, making diagnosis difficult. Therefore, it is typically found at an advanced stage, resulting in patients missing the opportunity for radical surgery. The complex biological characteristics of PC, coupled with the difficulties in drug delivery and tumor resistance, limit the effectiveness of drug therapy. Due to their compatibility with biological systems and low likelihood of triggering an immune response, exosomes are seen as a promising method for drug delivery. They are capable of targeting and penetrating tissues inside the body and can be engineered through surface modification and drug loading. Engineered exosomes possess controllable and diverse drug-carrying capabilities, which can enhance drug internalization and cellular uptake. Owing to their special properties and the potential to overcome the drawbacks of standard therapies, engineered exosomes have appeared as a promising treatment option. This review aims to comprehensively summarize the current application status and progress of engineered exosomes used in PC therapy.

Keywords:  Cancer therapy; Delivery system; Engineered exosomes; Pancreatic cancer

DOI:  https://doi.org/10.1186/s12951-025-03697-0
Nat Commun. 2025 Sep 30. 16(1): 8696

Engineered exosomes with KrasG12D specific siRNA in pancreatic cancer: a phase I study with immunological correlates.

Valerie S Kalluri, Brandon G Smaglo, Krishnan K Mahadevan, Michelle L Kirtley, Kathleen M McAndrews, Mayela Mendt, Sujuan Yang, Ana S Maldonado, Hikaru Sugimoto, Maria E Salvatierra, Luisa M Solis Soto, Cara Haymaker, Rick Finch, Mihai Gagea, Adam C Fluty, Steven J Ludtke, J Jack Lee, Abhinav K Jain, Gauri Varadhachary, Rachna T Shroff, Anirban Maitra, Elizabeth Shpall, Shubham Pant, Raghu Kalluri.

Oncogenic KRAS is amongst the key genetic drivers for initiation and maintenance of pancreatic ductal adenocarcinoma (PDAC). Here, we show that engineered exosomes with KrasG12D specific siRNA (iExoKrasG12D) reveal a biodistribution in pancreas with negligible toxicity in preclinical studies in mice and Rhesus macaques. Clinical testing of iExoKrasG12D in the iEXPLORE (iExoKrasG12D in Pancreatic Cancer) Phase I study employed a non-randomized single-arm classical 3 + 3 dose escalation design (Phase Ia), followed by an accelerated titration design (Phase Ib) (NCT03608631). The primary outcomes included safety, tolerability and target engagement, and the secondary outcomes aimed to assess disease control. Patients with advanced metastatic disease were enrolled after failure of multiple lines of therapy. iExoKrasG12D therapy was well-tolerated: the primary outcomes were met with iExoKrasG12D showing no dose-limiting toxicity. The maximum tolerated dose was not reached even at the highest dose. In some cases, iExoKrasG12D therapy was associated with stable disease response (secondary outcome). Downregulation of KRASG12D DNA and suppression of phospho-Erk was documented together with an increase in intratumoral CD8+ T cells following treatment. The CD8+ T cell recruitment priming by iExoKrasG12D informed on potential efficacy of immune checkpoint therapy and lead to validation testing in preclinical PDAC models. Combination therapy of iExoKrasG12D and anti-CTLA-4 antibodies, but not anti-PD1, revealed robust pre-clinical anti-tumor efficacy via FAS mediated CD8+ T cell anti-tumor activity. This first-in-human, precision medicine clinical trial and supporting preclinical functional studies offer new insights into priming of immunotherapy by oncogenic Kras inhibitor for future opportunistic combination therapy for PDAC patients.

DOI: https://doi.org/10.1038/s41467-025-63718-2
Curr Gene Ther. 2025 09 30.

Precision Medicine: Design of Immune Inert Exosomes for Targeted Gene Delivery.

Fawzy A Saad.

  Exosomes represent the smallest size among extracellular vesicles, which also include apoptotic bodies and microvesicles. Exosomes are natural nanocarriers that play a key role in intracellular communication, consisting of a hydrophobic lipid bilayer membrane and a hydrophilic core. The membrane compositions of exosomes are similar to those of the parent cells from which they are generated. Normally, the exosome membrane contains diacylglycerol, ceramide, cholesterol, and various surface proteins, including tetraspanins and Lamb2. Almost all cell types secrete exosomes into body fluids through exocytosis, including stem cells, epithelial cells, endothelial cells, immune cells, tumor cells, neurons, mast cells, oligodendrocytes, reticulocytes, macrophages, platelets, and astrocytes. Every cell type expresses a distinct type of exosomes carrying various bioactive molecules. Exosomes are major transporters of bioactive cargo, including enzymes, receptors, growth and transcription factors, nucleic acids, lipids, and other metabolites, which strongly affect the physiology of recipient cells. Exosomes are not only potent drug and gene delivery nanocarriers, but also have potential for disease diagnosis, tissue regeneration, and immunomodulation. Exosomes are present in various body fluids, including plasma, serum, saliva, milk, nasal secretions, urine, amniotic fluid, semen, and cerebrospinal fluid, among others. Stem cell-made exosomes are potential natural therapeutics, which is due to their rejuvenating cargo and ability to cross biological barriers. However, natural exosomes' inefficient cargo transfer and short lifespan in the bloodstream have hindered their progress in therapeutic interventions. Genetic engineering of the parent cell allows for loading specific therapeutic cargo into the lumen of newly generated exosomes and/or displaying certain homing peptides or ligands at their surface, leading to extension of their lifespan and precise delivery to specific organs or tissues. This minireview explores the creation of designer exosomes through parent cell engineering and their utilization for guiding the delivery of tailored therapeutic cargo to specific organs while evading the host's innate immune response.

Keywords:  Designer exosomes; extracellular vesicles; invisible exosomes; smart exosomes.; tailored cargos

DOI:  https://doi.org/10.2174/0115665232409032250908114520
Front Pharmacol. 2025 ;16 1635151

Modulation of ASC-derived extracellular vesicles containing cargo that specifically enhances wound healing.

Jodi P Gurney, John W Ludlow, Michael J Van Kanegan, Robin L Smith.

   Introduction: We have developed a bioreactor-based production system for manufacturing Human Adipose Stromal Cell (ASC) extracellular vesicles (EVs), which includes exosomes, using a highly controlled and tunable environment that can modify the cargo of these nanovesicles. The patented innovation focuses on engineering novel pro-healing EVs with therapeutic activity and using a topical formulation to treat diabetic ulcers.
Methods: To evaluate biological activity of tuned ASC EVs, functional activity assays were performed using human primary dermal fibroblast and keratinocyte culture models. Molecular and biochemical assays were used to assess cytokine regulation, collagen production and cell migration. Rodent wound healing models were used to assess therapeutic potential of modified exosomes. A Human volunteer case study was carried out with a consenting individual suffering from chronic diabetic ulcers.
Results: Herein we demonstrate that our proprietary engineered ASC EVs, eXo3 exosomes, contain a unique activity profile that reduces inflammatory cytokines, stimulates collagen production, as well as activates keratinocyte and fibroblast proliferation and migration. When formulated with an emollient and topically applied to an in vivo excisional wound model, tuned eXo3 exosomes demonstrated enhanced wound closure, increased keratinization, collagen deposition, and overall improved recover rate. In a clinical case study addressing non-healing diabetic foot ulcers, conducted under informed consent, topical treatment with tuned eXo3 exosomes formulated in a proprietary gel serum showed complete wound closure and dermal regeneration.
Conclusion: Our current research efforts have developed an EV manufacturing system that can be directed to improve the healing capacity of ASC-derived EVs. We show enhanced wound healing and repair activity in vitro and in vivo. Our data supports the regenerative properties of exosomes and reinforces their strong therapeutic potential.

Keywords:  adipose-derived stromal/stem cells; diabetic ulcer; exosomes; extracellular vesicles; mesenchymal stem cells; regenerative medicine; therapeutic vehicle; wound healing

DOI:  https://doi.org/10.3389/fphar.2025.1635151
Neural Regen Res. 2025 Sep 29.

M2 polarization of macrophages: Manipulation of spinal cord injury repair.

Yiran Lu, Hantian Yin, Lingwei Lou, Zhonglin Liu, Haiming Zhu, Chunyi Gu, Can Zhang, Junjuan Wang.

   ABSTRACT: Spinal cord injury results in lasting sensory and motor dysfunction with limited regenerative capacity. Macrophages play a crucial role in orchestrating secondary pathogenesis and repair mechanisms through polarization dynamics. Following spinal cord injury, these immune cells deploy context-dependent responses via divergent regulatory pathways, mediating phagocytic clearance, inflammatory modulation, and neural tissue remodeling. M1 macrophage polarization exacerbates tissue damage through cytokine storms, reactive oxygen species generation, and subsequent neuronal apoptosis, axonal fragmentation, and glial scarring. Conversely, dominant M2 polarization provides neuroprotection by resolving inflammation and promoting axonal sprouting. Strategic manipulation of macrophage plasticity is a promising frontier in spinal cord injury recovery therapy. This review comprehensively examines the regulatory mechanisms that govern macrophage polarization after spinal cord injury, the functional distinctions between resident microglia and peripheral macrophages, the pathophysiological cascades that occur across injury subtypes, and the emerging interventions that span nanotherapeutics, engineered exosomes, electroactive biomaterials, and photobiomodulation. However, there is still a lack of clinical therapies centered around macrophages due to a lack of human trials targeting macrophage reprogramming and excessive reliance on rodent models without validation in non-human primates. However, given the accelerated development of immunomodulatory biomaterials and the expanding mechanistic insights into polarization pathways, the precision targeting of macrophages warrants prioritized investigation for transformative spinal cord injury therapeutics.

Keywords:  activation; biomaterial; clinical trial; inflammatory; macrophage; neuron regeneration; polarization; spinal cord injury; therapeutic strategy; tissue repair

DOI:  https://doi.org/10.4103/NRR.NRR-D-24-01579
Br J Pharmacol. 2025 Sep 29.

Silencing the fibronectin gene (FN1) improves NaCl-induced cardiac fibrosis via ferritinophagy-mediated ferroptosis in a nuclear receptor coactivator 4 (NCOA4)-dependent manner.

Yawei Dai, Yong Li, Xiaoliang Yang, Yu Zhou, Yukang Mao, Yang Chuanxi, Peng Li, Kun Zhao.

   BACKGROUND AND PURPOSE: High-salt diet (HSD) induces heart damage, including cardiac fibrosis, independent of blood pressure. Exploring the underlying molecular mechanisms is of significant clinical value.
EXPERIMENTAL APPROACH: Male rats or neonatal rat cardiac fibroblasts (NRCFs) were treated with HSD or sodium chloride (NaCl) to induce cardiac fibrosis in vivo and in vitro, respectively. Exosome high-throughput sequencing was performed from exosomes isolated from culture supernatants of NRCFs treated with/without NaCl.
KEY RESULTS: First, HSD and NaCl induced myocardial fibrosis and ferroptosis in vivo and in vitro, respectively. The results of exosome high-throughput sequencing, along with validation experiments, showed that NaCl increased fibronectin gene (Fn1) expression via post-transcriptional regulation in NRCFs. Cardiac-specific silencing of Fn1attenuated HSD-induced cardiac fibrosis and ferroptosis, while Fn1 overexpression counteracted these effects. Also, GW4869-mediated exosome depletion reduced extracellular FN-1 but did not rescue NaCl-induced cardiac fibrosis. Moreover, silencing Fn1 inhibited NaCl-induced increase of nuclear receptor coactivator 4 (NCOA4). Fn1 loss exacerbated NCOA4 degradation. Next, inhibition of NOCA4-mediated ferritinophagy improved HSD-induced cardiac fibrosis, whereas NCOA4 overexpression hampered the antifibrotic effects of silencing Fn1in NaCl-induced NRCFs. Besides, autophagy inhibitor 3-MA ameliorated NaCl-induced cardiac fibrosis and ferroptosis, indicating that autophagy was essential for NCOA4-mediated ferroptosis.
CONCLUSION AND IMPLICATIONS: Overall, our finding identified that silencing Fn1 possessed beneficial effects against NaCl-induced cardiac fibrosis through downregulating the ferroptosis of NRCFs, which was attributed to the inhibition of NOCA4-mediated ferritinophagy.

Keywords:  cardiac fibrosis; ferritinophagy; ferroptosis; fibronectin; high‐salt diet (HSD)

DOI:  https://doi.org/10.1111/bph.70205
Int J Nanomedicine. 2025 ;20 11669-11683

How Advanced Are Exosomes as Cell-Free Therapeutics for Spinal Cord Injury?

Yaqi Wu, Yu Wang, Jun Zhou, Zhijian Tang, Lulu Huang, Shengwen Liu.

  Spinal cord injury (SCI) remains a leading cause of disability worldwide, characterized by complex pathophysiological processes involving primary mechanical damage and secondary cascades of inflammation, oxidative stress, and gliosis. Current cell-based therapies face challenges such as low survival rates, tumorigenicity, and immune rejection. Emerging evidence highlights exosomes-nanoscale extracellular vesicles derived from various cell types-as promising cell-free therapeutic agents. These exosomes mediate intercellular communication by transferring bioactive cargo and exhibit advantages such as low immunogenicity, stability, and blood-spinal cord barrier permeability. This review explores the neuroprotective roles of exosomes from diverse cellular sources in SCI repair. Key mechanisms include regulation of macrophage/microglia polarization, suppression of pyroptosis, promotion of vascularization, inhibition of glial scar formation and enhancement of axonal growth. Challenges remain in optimizing exosome yield, standardization, and clinical translation. Future directions emphasize multi-target therapies, biomarker exploration, and hybrid approaches combining exosomes from multiple. A combination of exosomes with biomaterials or stem cells would amplify the therapeutic effects and reduce the dosage of exosomes. This review underscores the potential of exosome-based therapies to revolutionize SCI treatment by addressing its multifaceted pathophysiology while circumventing risks associated with cell transplantation.

Keywords:  axonal regeneration; exosomes; macrophage polarization; neuroprotection; spinal cord injury

DOI:  https://doi.org/10.2147/IJN.S536652
Int J Biol Macromol. 2025 Sep 25. pii: S0141-8130(25)08476-4. [Epub ahead of print]329(Pt 2): 147919

Mesenchymal stromal cell secretome in scaffold-based drug delivery: Advances, applications, and future directions.

Praveen Ramakrishnan, Abdulkadhar Mohamed Jalaludeen, Saranya Vinayagam, Lalitha Gnanasekaran, Thirumurugan Durairaj, Rajaram Rajamohan, Thanigaivel Sundaram.

  The mesenchymal stromal cell (MSCs) secretome, comprising growth factors, cytokines, chemokines, and extracellular vesicles (exosomes), has emerged as a promising cell-free therapeutic approach in regenerative medicine. This review highlights recent advancements in integrating the MSC secretome with biomaterial scaffolds for drug delivery and tissue repair. The secretome's paracrine signaling promotes tissue regeneration, offering advantages over traditional cell-based therapies by reducing immune risks and enhancing scalability. Scaffold systems such as hydrogels, electrospun nanofibers, and 3D-printed constructs have been designed to encapsulate the MSC secretome or exosomes, enabling controlled and localized delivery. Loading strategies, including surface adsorption, hydrogel embedding, microsphere encapsulation, and lyophilization, are employed to optimise release kinetics. MSC-derived exosomes, in particular, serve as efficient nanoscale carriers, enhancing bioavailability and protecting therapeutic cargo. Preclinical studies demonstrate the efficacy of secretome-integrated scaffolds in wound healing, cartilage repair, angiogenesis, antifibrotic therapy, neuroprotection, and tumour targeting. While the approach shows strong therapeutic promise, challenges such as production standardization, batch variability, targeting specificity, and regulatory constraints remain. Ongoing research in scaffold engineering and secretome optimization is essential to overcome these barriers and support clinical translation. Overall, MSC secretome-integrated scaffolds represent a safe, effective, and scalable strategy for regenerative therapy.

Keywords:  Biomaterials; Controlled release; Cytokines; Exosomes; MSC Secretome; Regenerative medicine; Scaffold-based delivery

DOI:  https://doi.org/10.1016/j.ijbiomac.2025.147919
Front Med Technol. 2025 ;7 1657594

The utilization of exosomes in hydrogels: a bibliometric analysis of publications from 2015 to May 2025.

Said El Turk, Abdulrahim A Sajini, Haider Butt.

  This paper is a bibliometric analysis of the utilization of exosomes in hydrogels for various applications, conducted by assessing the relevant documents in this evolving field of research. Since targeted drug delivery, cell communication, and tissue regeneration are of high importance in the field of biomedicine and medical sciences, incorporating exosomes can offer a valuable addition in such applications due to their high bioactivity and biocompatibility. Applications include ocular drug delivery, boosting optic nerve damage, and disease detection, such as cancer and diabetes. Exosome-based technologies have been of interest since the mid-2000s, with an increased momentum in recent years. In this study, data were exported from the Web of Science and Scopus databases and plotted in order to identify the research trends and publication impact in such an evolving area. The analysis reveals that among several countries, China has the greatest number of publications within the period of 2015 to 9th-11th of May 2025, with a contribution of approximately 76.21% and 61.92% based on the WOS and Scopus databases, respectively. Both publications and citation trends show a significant increase with time, reflecting the increased interest in this field. This study aims to provide an overview of the current impact of research on utilizing exosomes in hydrogel systems.

Keywords:  exosomes; extracellular vesicles; hydrogels; nanoparticles; polymers

DOI:  https://doi.org/10.3389/fmedt.2025.1657594
Biosens Bioelectron. 2025 Sep 25. pii: S0956-5663(25)00904-2. [Epub ahead of print]291 118028

Chemiluminescent optical fiber biosensing platform with tyramide signal amplification for ultrasensitive detection of tumor-derived exosomes.

Siqi Zhao, Shuangyu Tang, Bowen Chi, Jinlan Yang, Liande Zhu, Li Yang.

  Exosomes have emerged as promising non-invasive biomarkers in liquid biopsy for the early diagnosis and treatment of cancers. Traditional methods for exosome analysis are often limited by complex procedures and costly instruments, as well as challenges including low signal differentiation and interference from large amounts of free proteins in body fluids. Herein, we propose a novel biosensing platform that integrates tyramide signal amplification (TSA) with a lipid-anchored chemiluminescent optical fiber sensor (COFS). The platform utilizes distearoyl phosphatylethanolamine-polyethylene glycol (DSPE-PEG) as lipid-anchor to capture exosomes and horseradish peroxidase (HRP)-labeled aptamers for specific recognition. The dual identification of surface proteins and membrane structure avoids interference from free proteins. The TSA-based signal amplification system significantly enhances detection sensitivity, benefiting from the abundance of proteins in exosomal membranes that function as deposition sites for active tyramine. The proposed TSA-COFS platform offers a cost-effective solution to the challenges of exosome quantitation, enabling rapid analysis, ultrasensitive detection and point-of-care profiling of tumor-derived exosomes within biological samples. The efficacy of the platform was demonstrated by analyzing Mucin 1 protein (MUC1)-expressing exosomes from human clinical serum samples. The results show that the method can achieve rapid and accurate determination of exosomes with high selectivity and an extremely low limit-of-detection of 6.76 particles/μL. A home-made portable device, equipped with the sensor probe, a "plug-in" operation of the reagent strip, a battery-powered photon counter and a touch-screen computer, is used for the assays, demonstrating the potential practical value of the TSA-COFS for exosome quantitation and point-of-care testing (POCT) applications.

Keywords:  Chemiluminescent optical fiber sensor; Point-of-care testing; Tumor-derived exosomes; Tyramide signal amplification; Ultrasensitive detection

DOI:  https://doi.org/10.1016/j.bios.2025.118028
World J Stem Cells. 2025 Sep 26. 17(9): 106282

Bone marrow mesenchymal stem cell-derived exosomal lactate dehydrogenase A promotes tendon-bone healing via histone lactylation-mediated cartilage regeneration.

Ting Zhang, Qing Huang, Kai-Feng Gan.

   BACKGROUND: Anterior cruciate ligament reconstruction (ACLR) is the dominant clinical modality for the treatment of anterior cruciate ligament injuries. The success of ACLR is largely dependent on tendon-bone healing, and stem cell biotherapies are often used to facilitate this process. Histone lactylation modifications are involved in the regulation of various diseases. Lactate dehydrogenase A (LDHA) has been shown to play an important role in exosomes.
AIM: To explore the regulation of tendon-bone healing after ACLR by LDHA in exosomes derived from bone marrow mesenchymal stem cells (BMSC-Exos).
METHODS: BMSC-Exos and LDHA were characterized and analyzed by transmission electron microscopy, qNano, immunofluorescence and western blotting assay. The corresponding low expression cell lines were obtained using RNA interference transfection; LDHA expression in rat bone tissues after ACLR was analyzed by western blotting. The volume of newborn bone tissues was monitored by micro-computed tomography imaging. Tendon and fibrocartilage regeneration were further analyzed and calculated by histological analysis, including hematoxylin and eosin and Safranin O-Fast green staining, respectively; LDHA levels of chondrocyte stem cells (CSPCs) after co-incubation with BMSC-Exos were analyzed by western blotting. Extracellularly secreted lactic acid content was determined by lactate assay kit. Cell viability was assessed by cell counting kit 8 assay, and the proliferation and differentiation ability of cells was further examined by the expression of collagen II, SOX9 and aggrecan. Histone H3K18 lactylation modification was analyzed by western blotting. H3K18 La binding on bone morphogenetic protein 7 (BMP7) promoter was analyzed by chromatin immunoprecipitation-quantitative polymerase chain reaction; BMP7 promoter activity was analyzed by dual luciferase reporter gene; BMP7 protein expression was analyzed using quantitative polymerase chain reaction and western blotting. Then, the proliferation of CSPCs promoted by BMSC-Exos LDHA was analyzed by protein expression levels of LDHA, BMP7, collagen II, SOX9, aggrecan, extracellular lactate content, and cell counting kit 8 assay.
RESULTS: The spherical nanosized BMSC-Exos could be uptaken by CSPCs. LDHA was highly expressed in BMSC-Exos, which could infiltrate into the bone tissue of ACLR rats and promoted the generation of new bone tissue, as well as significantly increased the regeneration of tendon and fibrocartilage. Co-incubation of CSPCs with high-expressing LDHA BMSC-Exos increased the secretion of lactate content from CSPCs, cell viability, and the expression of markers related to cell proliferation and differentiation, including collagen II, SOX9, and aggrecan; LDHA in BMSC-Exos upregulated BMP7 through histone H3K18 lactate modification; high LDHA expression reversed the knockdown of BMP7, further increasing the proliferation and differentiation of CSPCs, thereby inducing cartilage formation.
CONCLUSION: LDHA in BMSC-Exos promotes BMP7 expression via H3K18 lactylation modification, which further promotes tendon-bone healing after ACLR.

Keywords:  Bone mesenchymal stromal cells; Cartilage fragments; Exosome; Histone lactylation modification; Lactate dehydrogenase A; Tendon-bone healing

DOI:  https://doi.org/10.4252/wjsc.v17.i9.106282
Mikrochim Acta. 2025 Sep 30. 192(10): 701

Enzyme-free quantification of breast cancer-derived exosomes via cubic DNA nanostructure-enhanced hybridization chain reaction.

Wenting Cheng, Jinhua Chen, Han Pan, Miao He, Yongliang Cai, Zhongyun Wang, Yang Xiang.

  Breast tumor-derived exosomes promise to guide diagnosis and therapy. But the small size and low mass of exosomes have higher requirements for target binding and signal amplification. Although hybridization chain reaction (HCR) has been extensively utilized for the sensitive detection of an enormous range of biomolecules, including the exosomes, achieving sufficient amplification efficiency remains challenging. To address this limitation, more and more researchers integrate the reaction system with functional materials of DNA. Inspired by this, we herein report for the first time the cubic DNA nanostructure enhanced hybridization chain reaction (CDN-HCR) to detect breast tumor-derived exosomes. Unlike other nanostructure-assisted HCR approaches, the four cholesterol anchors on the CDN enhance the binding affinity of signal probes for exosomes, while the four triggers combined with the supporting CDN further improve the reaction efficiency of HCR. Furthermore, incorporating an electrochemical detection system, the assay platform enables enzyme-free and label-free detection of exosomes. The quantitative detection of exosomes is easily achieved with a linear range of 5.5 × 102 to 5.5 × 107 particles/μL and a minimal detectable concentration of 51 particles/μL. Finally, the human serum study proves the feasibility of this technique in clinic applications.

Keywords:  Breast cancer–derived exosomes; Cubic DNA nanostructure; Differential pulse voltammetry; Electroanalysis; HCR

DOI:  https://doi.org/10.1007/s00604-025-07545-8
J Ovarian Res. 2025 Oct 01. 18(1): 216

Exosomes derived from mesenchymal stem cells repair ovarian function by suppressing NLRP3-mediated pyroptosis in cyclophosphamide-induced premature ovarian failure.

Xiangrong Cui, Huihui Li, Xia Huang, Tingting Xue, Shu Wang, Xinyu Zhu, Xuan Jing.

   BACKGROUND: Premature ovarian failure (POF) is a debilitating condition impairing fertility and health in women. Mesenchymal stem cell-derived exosomes (MSC-EVs) have emerged as a promising therapeutic option for POF due to their regenerative capabilities. This study explores the effectiveness of human umbilical cord mesenchymal stem cell-derived exosomes (HuMSCs-Exos) in counteracting NLRP3-mediated pyroptosis and restoring ovarian function in a cyclophosphamide (CTX)-induced POF model.
METHODS: HuMSCs-Exos were characterized using transmission electron microscopy (TEM), nanoparticle tracking analysis (NTA), and western blot for exosomal markers. A CTX-induced POF mouse model was treated with HuMSCs-Exos to assess their impact on ovarian morphology, function, and fertility. Additionally, in vitro studies on granulosa cells (GCs) evaluated the effects of HuMSCs-Exos on cell viability, apoptosis, oxidative stress, and NLRP3 inflammasome pathway components.
RESULTS: In the CTX-induced POF model, HuMSCs-Exos treatment significantly improved ovarian structure, increased follicle counts, restored estrous cycles, and enhanced fertility outcomes. Hormonal balance was also achieved, with a notable reduction in NLRP3 inflammasome activation and oxidative stress markers. In vitro, HuMSCs-Exos promoted GCs viability and reduced apoptosis and oxidative damage, further inhibiting the NLRP3 inflammasome pathway.
CONCLUSION: HuMSCs-Exos effectively mitigate CTX-induced POF through the suppression of NLRP3-mediated pyroptosis, enhancing ovarian function and fertility. This study underscores the potential of MSC-EV-based therapies for treating POF and possibly other inflammatory and degenerative reproductive disorders.

Keywords:  Cyclophosphamide (CTX); Exosomes; Human umbilical cord mesenchymal stem cells (HuMSCs); NLRP3 inflammasome; Premature ovarian failure (POF)

DOI:  https://doi.org/10.1186/s13048-025-01785-1