bims-engexo Biomed News
on Engineered exosomes
Issue of 2026–01–11
twelve papers selected by
Ravindran Jaganathan, Universiti Kuala Lumpur
  1. The Role of Exosomes as Endogenous Nanocarriers for Targeted Drug Delivery: Isolation, Engineering, and Clinical Progress in Neurological and Other Diseases.
  2. Hybrid exosomes: a rising horizon for precision cancer therapy.
  3. RVG-targeted extracellular vesicles loaded with echinatin attenuate dopaminergic neurodegeneration via the IGF-2/PI3K/Akt pathway in Parkinson's disease mice.
  4. Engineered Dll4-overexpressing osteocyte-derived exosomes enhanced bone regeneration by regulating osteogenesis and angiogenesis.
  5. NSUN2-engineered human umbilical cord mesenchymal stem cell-derived exosomes ameliorate tendon injury by promoting DNM2 expression.
  6. Endothelial-targeted modification of ginseng-derived exosomes for IL-6 SiRNA delivery ameliorates hepatic ischemia-reperfusion injury.
  7. Engineered outer membrane vesicles enhance solid tumour CAR-T cell therapy.
  8. Comparison of Different Encapsulation Techniques in Exosomes Obtained from Goat and Bovine Milk.
  9. Exosome-Enhanced Sonodynamic Therapy in Cancer: Emerging Synergies and Modulation of the Tumor Microenvironment.
  10. Targeted C3G delivery by engineered milk exosomes for effective therapy in microplastics-induced colitis.
  11. Engineered M2 macrophage-derived extracellular vesicles reprogram mitochondrial metabolism to alleviate temporomandibular joint cartilage degeneration.
  12. Exosomal NAMPT from Engineered Mesenchymal Stem Cells Mitigates Aortic Stenosis via Metabolic and Anti-Inflammatory Pathways.
  1. J Integr Neurosci. 2025 Dec 26. 24(12): 47443
    The Role of Exosomes as Endogenous Nanocarriers for Targeted Drug Delivery: Isolation, Engineering, and Clinical Progress in Neurological and Other Diseases.
    Xue-Qing Liu, Rui Sheng.
      Exosomes are extracellular vesicles that carry a variety of biomolecules, including nucleic acids, proteins, and lipids, and they play a vital role in intercellular communication. These endogenous carriers offer several advantages over conventional nanocarriers, such as liposomes. These advantages include high biocompatibility, low immunogenicity, and the ability to cross biological barriers such as the blood-brain barrier, making them a promising platform for targeted drug delivery. In this review, we systematically summarize the biological characteristics of exosomes, methods for their isolation and purification, strategies for drug loading (including endogenous and exogenous approaches), and surface engineering techniques (such as genetic engineering and chemical modification) to enhance targeting and therapeutic efficacy, based on a comprehensive PubMed literature search. We particularly focus on the modification of engineered exosomes as drug delivery systems in various clinical contexts, covering multiple diseases including cancer, diabetes, neurological diseases, cardiovascular diseases, and tissue repair. Administration routes include oral, subcutaneous, intranasal, and intravenous delivery. While exosomes have shown promise in preclinical studies, challenges remain in terms of large-scale production, standardized isolation, drug loading efficiency, and safety evaluation. Herein, we aim to provide a theoretical foundation and suggest future directions for developing exosomes as a next-generation drug delivery platform.
    Keywords:  blood-brain barrier; cardiovascular diseases; diabetes mellitus; drug delivery systems; exosomes; nanomedicine; neoplasms; translational medical research
    DOI:  https://doi.org/10.31083/JIN47443
  2. RSC Adv. 2026 Jan 02. 16(2): 1292-1309
    Hybrid exosomes: a rising horizon for precision cancer therapy.
    Swarup Sonar, Asmit Das, Sidhanti Nyahatkar, Rajib Dhar, Ketki Kalele, Vinod R M T Balasubramaniam, Ling Shing Wong, Vinoth Kumarasamy, Vetriselvan Subramaniyan.
      Extracellular vesicles (EVs) are nanoscale vesicles, which show significant promise as biomarkers for cancer diagnosis and prognosis, by providing valuable information about cancer progression and treatment response. Their therapeutic potential (including their popular subset: exosomes) is significant, but challenges remain. These limitations with natural exosomes, necessitate innovative engineering strategies. However, current methods for engineering exosomes, such as chimeric and surface modifications, still need to be improved. A prominent issue is drug off-targeting, leading to ineffective treatment and side effects. To address these challenges, "hybrid exosomes" have been engineered by combining the inherent biocompatibility of natural exosomes with the versatility of synthetic nanoparticles. Cutting-edge design strategies for hybrid exosomes, such as bio-hybrid approaches, emphasize their superior drug loading capacity, and targeted delivery to tumor sites, resulting in minimized toxicity profiles. Furthermore, we showcase recent breakthroughs in leveraging hybrid exosomes for the effective delivery and cellular uptake of chemotherapeutic agents and immunotherapies, which offer significantly enhanced therapeutic outcomes in preclinical cancer models, with emerging clinical relevance. This review explores the evolving field of hybrid exosomes, a novel approach to cancer therapeutics and highlights their potential to overcome existing limitations in cancer treatment. Hybrid exosomes offer a transformative approach to cancer treatment, promising affordable and effective precision therapy with a significant impact on cancer therapeutics.
    DOI:  https://doi.org/10.1039/d5ra04927j
  3. J Nanobiotechnology. 2026 Jan 07.
    RVG-targeted extracellular vesicles loaded with echinatin attenuate dopaminergic neurodegeneration via the IGF-2/PI3K/Akt pathway in Parkinson's disease mice.
    Liuyan Ding, Yuchen Xiao, Zongtang Xu, Ziting Zhu, Tingting Gan, Xingting Huang, Hui Shu, Xiaolei Liang, Mingshu Mo, Xiaoyun Huang, Xiaoqin Zhu, Weiqing Huang, Pingyi Xu, Wenlong Zhang.
       BACKGROUND: Parkinson's disease (PD) is a progressive neurodegenerative disorder characterized by the loss of dopaminergic (DA) neurons. The development of effective neuroprotective therapies is severely hampered by the blood-brain barrier (BBB), which restricts drug delivery to the central nervous system. This study aimed to develop a novel brain-targeted nanodelivery system by functionalizing extracellular vesicles (EVs) with a rabies virus glycoprotein (RVG)-derived peptide to deliver echinatin (Echi), and to systematically evaluate its therapeutic efficacy and underlying mechanisms in a mouse model of PD.
    RESULTS: We successfully engineered the nanotherapeutics, termed RVG-EVs@Echi, which efficiently crossed the BBB and selectively accumulated in DA neurons and microglia following systemic administration. In a chronic MPTP-induced mouse model of PD, treatment with RVG-EVs@Echi significantly ameliorated motor deficits and rescued tyrosine hydroxylase (TH)-positive neurons in the substantia nigra and striatum, with no detectable peripheral toxicity. Mechanistically, RVG-EVs@Echi exerted potent neuroprotective effects by upregulating insulin-like growth factor-2 (IGF-2) and activating the downstream PI3K/Akt/Nrf2 signaling cascade, which mitigated oxidative stress and neuronal apoptosis. Furthermore, integrated multi-omics analyses revealed that RVG-EVs@Echi treatment modulated metabolic profiles in the midbrain and gut, and partially restored MPTP-induced gut microbiota dysbiosis.
    CONCLUSIONS: This study demonstrates that RVG-EVs@Echi represents a safe, noninvasive, and effective nanotherapeutic platform for targeted brain delivery in PD. By activating the IGF-2/PI3K/Akt/Nrf2 neuroprotective pathway and modulating the gut-brain metabolic axis, this targeted delivery system presents a highly promising and translatable strategy for the treatment of PD and other neurodegenerative diseases.
    Keywords:  Blood–brain barrier penetration; Echinatin; Engineered extracellular vesicles; IGF2; Neuroprotection; Parkinson's disease; RVG peptide
    DOI:  https://doi.org/10.1186/s12951-025-03997-5
  4. Theranostics. 2026 ;16(6): 2780-2797
    Engineered Dll4-overexpressing osteocyte-derived exosomes enhanced bone regeneration by regulating osteogenesis and angiogenesis.
    Yujie Yan, Pengtao Wang, Xi Tang, Yuhang Wang, Mengting Xiao, Zhenbao Liu, Xiaolin Tu, Xian Li.
      Rationale: Delayed fracture healing often results from impaired osteocyte network reconstruction and inadequate vascularization. Our prior work demonstrated that osteocytes engineered to overexpress Dll4 (Dll4-osteocytes) exert dual pro-osteogenic/angiogenic effects. Thus, this study explores the exosomes derived from Dll4-osteocytes (Dll4-Exo) as a cell-free strategy to coordinate bone-vascular regeneration and accelerate repair. Methods: Dll4-Exo were isolated from lentivirus-transduced Dll4-osteocytes. Mouse bone marrow stromal cells (ST2 cells) and human umbilical vein endothelial cells (HUVECs) were treated with Dll4-Exo to evaluate osteogenesis (ALP staining, mineralization, qRT-PCR) and angiogenesis (scratch/transwell migration, tube formation). Notch dependence was tested with γ-secretase inhibitor DAPT. In vivo, Dll4-Exo was locally administered in a mouse tibial fracture model. Healing was assessed via X-ray imaging, histology, immunohistochemistry, and immunofluorescence staining at days 14, 21, and 28. Exosomal miRNA profiles were analyzed by sequencing, and miR-23a-5p function was validated through mimic/inhibitor transfections. Results: Dll4-Exo activated Notch signaling in ST2 cells, significantly upregulating osteogenic genes (Alpl: 9.4-fold increase; mineralization: 62% increase) and enhancing HUVEC migration (2.6-fold) and tube formation. In the fracture model, Dll4-Exo accelerated callus formation, improved bone remodeling (OCN: 1.52-fold increase), and promoted revascularization (CD31⁺ vessel density: 1.56-fold increase with enhanced maturity). Through miRNA sequencing, miR-23a-5p was identified as the most enriched miRNA in Dll4-Exo, which was functionally transferred to both ST2 cells (3.0-fold increase) and HUVECs (2.7-fold increase). Mechanistic studies demonstrated that the pro-osteogenic effect of Dll4-Exo is exerted by miR-23a-5p via Notch signaling activation in ST2 cells, whereas its pro-angiogenic effect on HUVECs occurs through miR-23a-5p-independent mechanisms. Conclusion: Dll4-Exo carrying miR-23a-5p activates Notch-dependent osteogenesis in ST2 cells, while stimulating angiogenesis in HUVECs through alternative mechanisms, synergistically accelerating fracture healing and osteocyte network reconstruction. This engineered exosome platform represents a clinically viable strategy for bone regeneration.
    Keywords:  Dll4-overexpressing osteocytes; Notch signaling.; angiogenesis; exosome; osteogenesis
    DOI:  https://doi.org/10.7150/thno.121905
  5. Regen Ther. 2026 Mar;31 101050
    NSUN2-engineered human umbilical cord mesenchymal stem cell-derived exosomes ameliorate tendon injury by promoting DNM2 expression.
    Yuxin Liu, Yalu Pu, Qi Li, Liang Yu, Hailong Kou, Yang Liu, Zhizhong Shen, Yilei Zhao.
       Background: Tendon injuries are a common musculoskeletal problem, often leading to chronic pain and disability. Current treatment options, including surgical interventions and physical therapy, have limitations in terms of efficacy and potential complications. Human umbilical cord mesenchymal stem cells (HUCMSCs) are a promising source of mesenchymal stem cells (MSCs), and exosomes derived from HUCMSCs have been shown to mediate various biological processes. This study aims to investigate the role of HUCMSC-derived exosomes in tendon injuries and the underlying mechanism.
    Methods: Exosomes were isolated from HUCMSCs using differential centrifugation. Cell viability was assessed using a cell counting kit-8 assay. Cell proliferation was measured by a 5-Ethynyl-2'-deoxyuridine assay. Transwell invasion assays were conducted to analyze cell invasion, and wound-healing assays were used to evaluate cell migration. Quantitative real-time PCR (qRT-PCR) was employed to analyze DNM2 mRNA expression. Western blotting was used to detect the protein expression of NOP2/Sun RNA methyltransferase 2 (NSUN2), C cluster of differentiation 63 (CD63), CD81, and dynamin 2 (DNM2). m5C methylated RNA immunoprecipitation and RNA immunoprecipitation (RIP) assays were performed to analyze the association of NSUN2 with DNM2. Additionally, an RIP assay was conducted to study the interaction among Y-box binding protein 1 (YBX1), NSUN2, and DNM2 in injured tenocytes. Rats were subjected to superficial tendon excision and partial transection of the deep Achilles tendon to induce tendon injury. Hematoxylin and eosin (HE) staining was used to analyze the pathological conditions of Achilles tendon tissues, and an immunohistochemistry (IHC) assay was performed to detect the positive expression rates of NSUN2 protein.
    Results: HUCMSC-derived exosomes significantly promoted the proliferation, migration, and invasion of injured tenocytes. Overexpression of NSUN2 also enhanced the proliferative, migratory and invasive abilities of injured tenocytes. The exosomes derived from NSUN2-overexpressing HUCMSCs showed a more pronounced promoting effect on injured tenocyte proliferation, migration, and invasion compared to control exosomes. NSUN2 stabilized DNM2 mRNA expression through m5C methylation modification. YBX1 interacted with NSUN2 to stabilize DNM2 expression. In addition, knockdown of DNM2 attenuated the promoting effects of HUCMSC-derived exosomes with NSUN2 overexpression on the proliferation, migration, and invasion of injured tenocytes. Moreover, exosomes derived from NSUN2-overexpressing HUCMSCs improved tendon injury in a rat model, as indicated by enhanced pathological conditions within the tendon tissues.
    Conclusion: HUCMSC-derived exosomal NSUN2 played a crucial role in ameliorating tendon injury by promoting DNM2 expression. The findings suggest that exosomes from NSUN2-overexpressing HUCMSCs could serve as a novel therapeutic strategy for tendon repair and regeneration.
    Keywords:  DNM2; Exosomes; HUCMSCs; NSUN2; Tendon injury
    DOI:  https://doi.org/10.1016/j.reth.2025.101050
  6. J Nanobiotechnology. 2026 Jan 05. 24(1): 22
    Endothelial-targeted modification of ginseng-derived exosomes for IL-6 SiRNA delivery ameliorates hepatic ischemia-reperfusion injury.
    Kaijun Huang, Xuanlin Zhang, Xufeng Yan, Meiting Qin, Linpei Lv, Shuangqin Yang, Yang Zheng, Guohao Yin, Xinyu Tian, Xueyun Wang, Wenjing Deng, Yaning Yan, Wenjing Wu, Haoxiang Yuan, Zhijin Fan, Chunming Wang, Jian Ma.
      Liver ischemia-reperfusion injury (IRI) serves as a critical pathological basis for post-hepatectomy liver failure and graft dysfunction following liver transplantation. Excessive inflammatory responses, oxidative stress, and cell death are key mechanisms underlying IRI. The lack of multi-targeted therapies contributes to the current insufficiency in clinical IRI management. This study developed endothelial-targeting VHPKQHR peptide (VHP)-modified ginseng-derived exosomes (G-Exos) loaded with IL-6 small interfering RNA (Si-IL6) (siRNA@VG-Exos) to mitigate liver IRI. VHP modification facilitated the targeted delivery of siRNA@VG-Exos to damaged endothelium, promoting their accumulation and subsequent release at the IRI site. siRNA@VG-Exos effectively reduced hepatic inflammatory cytokine release, enhanced T-SOD and CAT expression while suppressing MDA generation, thereby alleviating oxidative stress. Furthermore, they promoted the restoration of mitochondrial membrane potential, maintaining mitochondrial homeostasis. Si-IL6 additionally suppressed IL-6 expression in liver tissue, synergistically enhancing the anti-inflammatory effect of G-Exos. Moreover, siRNA@VG-Exos inhibited CD86 expression and promoted CD206 expression in hepatic macrophages, facilitating their polarization from the pro-inflammatory M1 phenotype to the anti-inflammatory M2 phenotype and modulating immunity. Ultimately, siRNA@VG-Exos reduced hepatic necrotic areas, lowered ALT and AST levels, and restored liver tissue function. Further sequencing analysis indicated that siRNA@VG-Exos alleviates liver IRI by inhibiting immune and inflammatory responses and oxidative stress damage. Therefore, siRNA@VG-Exos provides a novel targeted strategy for the treatment of liver IRI.
    Keywords:  Ginseng-derived exosomes; Hepatic macrophages; Inflammatory response; Liver ischemia-reperfusion injury; Oxidative stress
    DOI:  https://doi.org/10.1186/s12951-025-03954-2
  7. Nat Biomed Eng. 2026 Jan 07.
    Engineered outer membrane vesicles enhance solid tumour CAR-T cell therapy.
    Xianjun Li, Xuehan Li, Jiaqi Shi, Yingjing Li, Hanyu Zhang, Tianjun Chen, Hui Pang, Shuyuan Zhang, Shengnan Luo, Fengyi Liu, Shuang Li, Chujie Ding, Linlin Sun, Fan Xing, Tongsen Zheng.
      Major challenges facing chimeric antigen receptor (CAR)-T cell therapy for solid tumours include the immunosuppressive tumour microenvironment and the heterogeneity of antigen expression. Bacterial outer membrane vesicles (OMVs) naturally activate the immune system and can be engineered for drug delivery. Here we develop a bacterial OMV-based immunosuppression reversal and optimized antigen decoration platform for CAR-T therapy (BROAD-CAR), in which OMVs are modified to express a high-affinity anti-PD-L1 antibody and load plasmids encoding the target antigen for CARs. By blocking the PD-1/PD-L1 signalling pathway, our tumour-targeting platform enhances the antitumour activity of CAR-T cells both in vitro and in vivo and boosts CAR-T cell expansion by ameliorating the tumour microenvironment. BROAD-CAR also facilitates the in situ antigenic modification of solid tumours and achieves CAR-mediated lysis of antigen-heterogeneous and antigen-negative tumours, inhibiting tumour recurrence and metastasis in the breast cancer mouse models. Our findings highlight a safe and efficient approach to enhance the efficacy and applicability of CAR-T therapy in solid tumours.
    DOI:  https://doi.org/10.1038/s41551-025-01575-6
  8. ACS Omega. 2025 Dec 30. 10(51): 63202-63212
    Comparison of Different Encapsulation Techniques in Exosomes Obtained from Goat and Bovine Milk.
    Mariana Cavalcante Theophilo Gaspar de Oliveira, Helen Paula Silva Costa, Daniel Teixeira, Daniele Oliveira Bezerra Sousa, Carla Renata Figueiredo Gadelha, Maria Izabel Florindo Guedes, Maurício Fraga van Tilburg.
      Exosomes are the smallest extracellular vesicles and can transport several molecules between cells. Mammalian milk is a significant source of exosomes. The aim of this study was to isolate exosomes from goat milk (GM) and cow milk (CM) to compare their properties and their capacities for loading with bioactive compounds. Exosomes were purified by differential ultracentrifugation and morphologically characterized by scanning electron microscopy (SEM) and dynamic light scattering (DLS). Moringa oleiferachitin-binding protein (Mo-CBP3) conjugated with FITC was charged into the vesicles by four different active methods: (1) electroporation, (2) sonication, (3) freeze-thaw cycles, and (4) incubation at room temperature in the presence of saponin. DLS analysis showed no significant difference between the diameters of the two exosome species. All methods of protein charging were effective. The in vitro cell assay also confirmed successful endocytosis of exosomes from both species by HepG2 cells, particularly those loaded using the freeze-thaw cycle and sonication methods. Goat milk is a viable alternative for encapsulating and delivering bioactive molecules.
    DOI:  https://doi.org/10.1021/acsomega.5c09524
  9. Cancers (Basel). 2025 Dec 30. pii: 118. [Epub ahead of print]18(1):
    Exosome-Enhanced Sonodynamic Therapy in Cancer: Emerging Synergies and Modulation of the Tumor Microenvironment.
    Giulia Chiabotto, Marzia Conte, Valentina Cauda.
      The development of safer, more effective, and tumor-specific therapeutic strategies remains a major challenge in oncology. Conventional treatments such as chemotherapy and radiotherapy often cause severe side effects and are limited in their ability to target deep-seated or resistant tumors. In this context, sonodynamic therapy (SDT) has emerged as a promising, non-invasive option, harnessing low-intensity ultrasound to activate sonosensitizers deep within tissues and generate cytotoxic reactive oxygen species (ROS) that selectively induce cancer cell death. Interestingly, SDT can also be combined with other therapies to achieve synergistic effects. However, despite encouraging preclinical results, SDT clinical translation is hindered by the poor aqueous solubility, instability, and low tumor specificity of traditional sonosensitizers. To overcome these limitations, recent studies have focused on employing extracellular vesicles (EVs), especially exosomes, as natural, biomimetic nanocarriers for sonosensitizer delivery. EVs offer unique advantages, including high biocompatibility, low immunogenicity, and intrinsic tumor-targeting ability, which make them ideal platforms for improving the therapeutic precision of SDT. Although several delivery strategies have been proposed, a comprehensive and focused overview of approaches specifically designed to enhance SDT performance using EVs is currently lacking. This review summarizes recent advances in integrating EVs with SDT for cancer treatment. It discusses the mechanisms underlying SDT, the engineering strategies developed to enhance exosome functionality, and the synergistic effects achieved through this combination. Furthermore, this review emphasizes that EV-based SDT not only enhances tumor accumulation of the therapeutic nanoplatforms, but also actively remodels the tumor microenvironment by improving oxygen availability, reversing immunosuppressive conditions, and triggering durable antitumor responses. Finally, the review addresses the translational challenges and outlines the critical future directions required to advance this promising therapeutic approach toward clinical application.
    Keywords:  cancer; exosomes; extracellular vesicles; sonodynamic therapy; tumor microenvironment
    DOI:  https://doi.org/10.3390/cancers18010118
  10. Mater Today Bio. 2026 Feb;36 102639
    Targeted C3G delivery by engineered milk exosomes for effective therapy in microplastics-induced colitis.
    Yuanjie Wu, Wen Chen, Xiang Ye, Xingkai Hao, Yuhao Wen, Jian Wu, Danyang Li, Lizhou Xu.
      Microplastic polystyrene (PS) ingestion through the food chain induces chronic colitis, with no effective intervention strategy, posing a public health concern globally. Cyanidin-3-O-glucoside (C3G), an anthocyanin abundant in red bayberry, can alleviate colitis while has limited therapeutic efficacy due to its low colonic bioavailability after oral administration. Targeted delivery strategies may enhance colonic C3G concentration and improve its therapeutic efficacy. Exosomes are engineerable nanoparticles with excellent biocompatibility and unique biological activities. In this study, the mucosal addressin cell adhesion molecule 1 (MAdCAM-1, F6) antibody, which specifically binds to colonic inflammatory MAdCAM-1 marker, was conjugated to the raw milk derived-exosome surface to form C3G@Exo-F6, aiming to enhance colonic C3G targeting. In vitro, C3G@Exo-F6 exhibited significantly enhanced stability in simulated digests and was more efficiently taken up by colon cells. In a PS-induced in vivo chronic colitis mice model, C3G@Exo-F6 demonstrated superior efficiency compared to C3G only by inhibiting inflammatory responses, restoring gut barriers integrity and modulating the gut microbiota. Mechanically, 16S rRNA sequencing and untargeted metabolomics demonstrated that C3G@Exo-F6 significantly increased the Lactobacillus abundance and subsequently upregulated the metabolic L-Proline level. Molecular docking identified that L-Proline binds effectively to nuclear receptor subfamily 1 group D member 1 (NR1D1) protein, inhibiting the expression of inflammatory TLR-4/COX-2 pathway. Additionally, Exo-F6 carries exhibited similar therapeutic effects, indicating that exosomes derived from raw milk possess collaborative anti-inflammatory activities. Collectively, these findings emphasize the potential of C3G@Exo-F6 for targeted treatment of chronic colitis, providing a food-derived therapeutic approach for microplastics-induced colonic inflammation.
    Keywords:  Chemical modification; Chronic colitis; Cyanidin-3-O-glucoside; Gut microbiome; Raw milk derived-exosomes
    DOI:  https://doi.org/10.1016/j.mtbio.2025.102639
  11. Mater Today Bio. 2026 Feb;36 102674
    Engineered M2 macrophage-derived extracellular vesicles reprogram mitochondrial metabolism to alleviate temporomandibular joint cartilage degeneration.
    Weiwen Ge, Lei Qi, Yun Wang, Jing Wang, Xin Fang, Shixue Lei, Dan Lin, Lei Zhang, Shanyong Zhang.
      Temporomandibular joint osteoarthritis (TMJOA) is a degenerative joint disease characterized by progressive degradation of the cartilage matrix. Current clinical interventions mainly offer symptomatic relief but fail to halt disease progression. The pathogenesis of TMJOA is driven by mitochondrial dysfunction, which promotes both chondrocyte inflammation and extracellular matrix breakdown. To address these issues, an integrated therapeutic system was developed by encapsulating curcumin into M2 macrophage-derived extracellular vesicles (Cur@M2-EVs) through ultrasonic processing. In vitro studies demonstrated that Cur@M2-EVs effectively attenuated inflammatory responses and cartilage matrix degradation by scavenging reactive oxygen species (ROS), restoring mitochondrial membrane potential, and shifting cellular metabolism from glycolysis back to oxidative phosphorylation. Furthermore, transcriptomic analysis and experimental validation revealed that Cur@M2-EVs alleviate chondrocyte inflammation primarily by suppressing Thbs1 expression. To enable sustained drug release and enhance joint lubrication, Cur@M2-EVs were further encapsulated within poly (ethylene glycol) diacrylate (PEGDA) hydrogel microspheres, forming the Cur@M2-EVs@PEGDA system. In a monosodium iodoacetate (MIA)-induced rat model of TMJOA, intra-articular injection of Cur@M2-EVs@PEGDA microspheres significantly alleviated cartilage destruction and improved joint lubrication. This study proposes a novel disease-modifying strategy for TMJOA treatment by integrating mitochondrial regulation, immunomodulation, and sustained lubricating release within a single platform, offering a promising therapeutic approach for this challenging condition.
    Keywords:  ECM degradation; Engineered extracellular vesicles; Hydrogel microspheres; Mitochondria metabolism; TMJOA; Temporomandibular joint osteoarthritis
    DOI:  https://doi.org/10.1016/j.mtbio.2025.102674
  12. Int J Mol Sci. 2025 Dec 25. pii: 256. [Epub ahead of print]27(1):
    Exosomal NAMPT from Engineered Mesenchymal Stem Cells Mitigates Aortic Stenosis via Metabolic and Anti-Inflammatory Pathways.
    Dipan Kumar Kundu, Matthew Kiedrowski, James Gadd, Min Gao, Madeline Evan, Yang Wang, Liya Yin, Vahagn Ohanyan, William M Chilian, Feng Dong.
      The aim of this study was to determine whether exosomes from Nicotinamide phosphoribosyltransferase (NAMPT)-overexpressing mesenchymal stem cells (MSC NAMPT-Exo) can attenuate aortic stenosis (AS) and explored the underlying mechanism. NAMPT expression was examined in EC CXCR4 KO (AS) mouse hearts. Six-week-old AS mice received weekly injections of NAMPT-Exo, MSC-Exo, or PBS for three weeks, followed by echocardiography and histological examination of the valves (H&E, Alizarin Red, immunofluorescence). Cardiac ECs from control, AS, and NAMPT-Exo-treated mice were analyzed for miRNA expression (miR-146a-3p/5p, miR-125b-5p, miR-142a-5p). NAMPT expression was decreased in AS hearts. Treatment with NAMPT-Exo reduced aortic valve peak velocity, valvular thickening, and microcalcifications, while improving ejection fraction, fractional shortening, and ventricular dimensions. AS endothelial cells showed elevated levels of miR-146a-3p, miR-146a-5p, and miR-142a-5p, NAMPT-Exo specifically normalized miR-146a-3p. Histology revealed EndMT in AS valves, which was diminished by NAMPT-Exo. In vitro, inhibiting miR-146a-3p suppressed TGF-β-induced EndMT. Our results demonstrate that NAMPT-enriched MSC-derived exosomes effectively slow the progression of AS. Additionally, our findings highlight miR-146a-3p as a key regulator of EndMT, suggesting it as a potential molecular target for future therapies.
    Keywords:  NAMPT; aortic stenosis; cardiovascular regeneration; cell-free therapy; endothelial dysfunction; extracellular vesicles; fibrosis; inflammation; metabolic modulation; valve calcification
    DOI:  https://doi.org/10.3390/ijms27010256
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