bims-engexo Biomed News
on Engineered exosomes
Issue of 2025–10–12
twelve papers selected by
Ravindran Jaganathan, Universiti Kuala Lumpur
  1. Engineered exosomes conferred with ROS-regulation and immuno-suppression for ameliorating lupus nephritis.
  2. Exosomes in pancreatic islet biology and diabetes: Mechanisms, Biomarkers, and potential therapeutic perspectives.
  3. Dual-ligand engineered exosome regulates WNT signaling activation to promote liver repair and regeneration.
  4. Exosome-based therapeutics in bone regeneration: from fundamental biology to clinical translation.
  5. Experimental Study on the Inhibitory Effect of Eupatilin on Osteosarcoma by the NBR2/miR-129-5p/FKBP11 Regulatory Axis.
  6. microRNAs shuttled by mesenchymal stromal cell-derived exosomes in coronary artery disease: A systematic review of preclinical studies.
  7. Exosomal microRNAs: A new role in the diagnosis and treatment of lung cancer metastases (Review).
  8. The roles of exosomes in the pathogenesis and treatment of coronary heart disease with depression and/or anxiety.
  9. Microneedles combining delivery of hUMSC-derived exosomes and EGCG mitigate UV-induced skin damage.
  10. Therapeutic effect of neural induced-stem cell-derived exosomes by regulating ERK/p38/NF-κB in traumatic brain injury.
  11. Platelet-Derived Transforming Growth Factor-β1: A New Hope for Cerebral Malaria Treatment.
  12. RNA-editing enzyme ADAR1 attenuates rheumatoid arthritis via regulating fibroblast-like synoviocytes-derived exosomal circFTO.
  1. J Nanobiotechnology. 2025 Oct 10. 23(1): 639
    Engineered exosomes conferred with ROS-regulation and immuno-suppression for ameliorating lupus nephritis.
    Jiang Tian, Zexin Wang, Zhicheng Tang, Haofang Zhu, Lingyun Sun.
      Mesenchymal stromal cell-derived exosomes (MEXs) possess inherent homing capabilities, tissue repair abilities, and anti-inflammatory and immunomodulatory functions, making them a promising alternative for treating lupus nephritis (LN). In this study, we present an innovative engineered MEX that serves both as a reactive oxygen species (ROS) scavenger and a rapamycin carrier for targeted LN therapy. The nanohybrid (CEX@Rapa) was developed by chemically conjugating ceria (Ce) nanoparticles to rapamycin-loaded thiol-functionalized MEXs through a Michael addition reaction. The resulting nanohybrids demonstrate minimal toxicity, optimal drug loading efficiency, superior cellular uptake capability, and remarkable anti-oxidant, anti-damage, and anti-inflammatory properties. Upon systemic administration to MRL/lpr mice, these nanohybrids tend to accumulate and persist at the site of kidney inflammation, mitigating the excessive immune response and promoting kidney repair, leading to significant alleviation of LN symptoms through the independent and synergistic effects of MEXs, Ce nanoparticles, and rapamycin. Therefore, we believe that Ce-immobilized MEXs, as an enhanced drug nanocarrier with ROS-regulating and immunomodulatory capabilities, hold substantial promise for treating LN and other autoimmune diseases.
    Keywords:  Ceria; Exosomes; Homing; Lupus nephritis; MSCs
    DOI:  https://doi.org/10.1186/s12951-025-03731-1
  2. J Mol Histol. 2025 Oct 11. 56(5): 337
    Exosomes in pancreatic islet biology and diabetes: Mechanisms, Biomarkers, and potential therapeutic perspectives.
    Venkatesan Karthick, Rajkumar Thamarai, Singamoorthy Amalraj, Mani Suganya, Panneerselvam Suganya.
      Exosomes, nanosized extracellular vesicles ranging from 30 to 150 nm, have gained increasing attention as mediators of cell-to-cell communication. Within the islet microenvironment, exosomes mediate crosstalk among β-cells, immune cells, and endothelial cells, helping maintain islet integrity, modulate immune responses, and influence the progression of type 1 and type 2 diabetes. Because of their intrinsic role in cellular communication, exosomes are being explored as potential therapeutic tools. Engineered exosomes can be tailored to transport bioactive molecules, including insulin, peptides, or anti-inflammatory agents, directly to pancreatic cells. Such targeted delivery may enhance glycemic control while limiting immune-mediated β-cell destruction. Beyond therapy, exosomes are also being investigated as biomarkers, as their molecular cargo reflects disease-specific alterations, offering opportunities for early diagnosis and timely intervention. This review further examines the scope of exosome-based diagnostics and therapeutics, including advances in exosome engineering and stem cell-derived exosomal applications. Compared with conventional systems, exosomes offer superior targeting, fewer off-target effects, and low immunogenicity due to their natural biocompatibility. These attributes position exosomal therapy as a promising avenue for the development of personalized strategies in diabetes management. In addition, novel findings on exosomal microRNAs, proteins, and lipid components involved in β-cell survival, insulin signaling pathways, and islet inflammation are summarized. Together, these insights highlight the emerging relevance of exosome biology in understanding diabetes pathogenesis and shaping innovative therapeutic approaches.
    Keywords:  Diabetes mellitus; Exosomes; Islet biology; miRNAs; β-cell
    DOI:  https://doi.org/10.1007/s10735-025-10631-z
  3. Nat Commun. 2025 Oct 10. 16(1): 9019
    Dual-ligand engineered exosome regulates WNT signaling activation to promote liver repair and regeneration.
    Lingyan Yang, Shixiang Wang, Zhiping Qiao, Yue Liu, Xu Wang, Liying Liu, Chunfang Yang, Jiying Ding, Miao Lei, Jiayi Zheng, Wenxiang Hu, Ye-Guang Chen, Yun-Shen Chan.
      WNT signaling is an essential pathway regulating tissue morphogenesis and regeneration. However, harnessing the pathway for regenerative medicine has been challenging due to the lack of approaches to identify and deliver specific WNT ligands to the target tissue. Herein, we reported that WNT and R-spondin (RSPO) proteins could be transported on engineered exosomes and activate the pathway synergistically. We showed that WNT3A and RSPO1 co-treatment could effectively regulate hepatic cell fate and uncovered functional crosstalk with the PPARα signaling pathway. Moreover, dual-ligand-carrying exosome (exoWNT3A/RSPO1) hyperactivated the WNT signaling and promoted efficient hepatic organoid growth compared to the small molecule inhibitor CHIR99021. Importantly, the exosome can be efficiently delivered for robust WNT signaling activation in the liver. Remarkably, exoWNT3A/RSPO1 could accelerate liver repair and regeneration under various conditions, including acute and chronic injuries and aging-associated phenotypes. Collectively, our work revealed the broad therapeutic effects of WNT signaling activation in the liver through the dual-ligand-carrying exosomes.
    DOI:  https://doi.org/10.1038/s41467-025-64069-8
  4. Stem Cell Res Ther. 2025 Oct 10. 16(1): 555
    Exosome-based therapeutics in bone regeneration: from fundamental biology to clinical translation.
    Fatemeh Tajafrooz, Sepehr Ghofrani, Fatemeh Sadeghghomi, Ali El Hadi Chamas, Narges Rahimi, Arshia Mirakhor, Mohammad Hosseini Hooshiar, Amir Raee.
      Bone deficiencies are a major clinical issue for millions worldwide, with challenges to treatment because of donor site morbidity, immunological rejection, and limited integration. Exosomes are endogenously secreted extracellular vesicles and have potential as cell-free therapeutics. Exosomes derived from mesenchymal stromal cells (MSCs), bone marrow cells, and other cell-derived exosomes transmit bone morphogenetic proteins, growth factors, and immunoregulatory microRNAs to initiate osteogenic pathways. These exosomes stimulate and orchestrate vascularization and bone formation. Engineering strategies such as cargo optimization, surface functionalization, and cellular preconditioning further augment therapeutic promise. Clinical translation for exosome therapy has hurdles in manufacturing standardization and regulatory routes.
    Keywords:  Biomaterial scaffolds; Bone regeneration; Exosomes; Mesenchymal stem cells; Tissue engineering
    DOI:  https://doi.org/10.1186/s13287-025-04686-8
  5. Ann Surg Oncol. 2025 Oct 07.
    Experimental Study on the Inhibitory Effect of Eupatilin on Osteosarcoma by the NBR2/miR-129-5p/FKBP11 Regulatory Axis.
    Xinzhe Zhang, Jihui Zhou, Jingtao Wu, Peng Yang, Guanghai Yuan.
       BACKGROUND: Osteosarcoma is a malignant bone tumor primarily composed of interstitial cells; there is an urgent need to develop effective treatments to improve patient prognosis. Traditional Chinese medicine offers a promising direction for research. This study explores the inhibitory effects and mechanisms of eupatilin on osteosarcoma, as well as the feasibility of using exosomes loaded with eupatilin in the treatment of osteosarcoma.
    METHODS: The cell counting kit-8 (CCK-8) assay was utilized to determine the optimal experimental concentration of eupatilin and assess its effect on cell proliferation. Cell apoptosis, migration, and invasion were evaluated through flow cytometry, wound healing assay, transwell assay, and colony formation assay. The expression of neighbor of BRCA1 gene 2 (NBR2), microRNA-129-5p (miR-129-5p), and FKBP prolyl isomerase 11 (FKBP11) were assessed using real-time quantitative polymerase chain reaction and Western blot. Extracellular exosomes from bone marrow mesenchymal stem cells were extracted via ultracentrifugation. Exosomes overexpressing miR-129-5p were obtained by transfecting the stem cells, and exosomes loaded with eupatilin were prepared through co-incubation. The inhibitory effects of different exosome treatments were observed.
    RESULTS: Cytological experiments demonstrated that eupatilin significantly enhances the apoptosis rate of osteosarcoma cells, suppresses cell viability, and markedly diminishes the capacities for colony formation, migration, and invasion. PCR and WB analyses revealed that the expression levels of NBR2, FKBP11 gene, and protein were notably reduced, whereas the expression level of miR-129-5p was significantly elevated. Exosome-based therapy exhibited a pronounced inhibitory effect on osteosarcoma cells.
    CONCLUSION: Eupatilin exerts a reliable inhibitory effect on osteosarcoma cells through the NBR2/miR-129-5p/FKBP11 regulatory axis. Exosomes can effectively carry both eupatilin and miR-129-5p, enhancing their therapeutic efficacy.
    Keywords:  Eupatilin; Exosomes; FKBP11; NBR2; Osteosarcoma; Tumor progression; miR-129-5p
    DOI:  https://doi.org/10.1245/s10434-025-18481-5
  6. Bioimpacts. 2025 ;15 30989
    microRNAs shuttled by mesenchymal stromal cell-derived exosomes in coronary artery disease: A systematic review of preclinical studies.
    Soroush Mostafavi, Amin Arasteh, Seyedeh Mina Mostafavi Montazeri, Seyyedeh Mina Hejazian, Farahnoosh Farnood, Sima Abediazar, Abolfazl Barzegari, Sepideh Zununi Vahed.
       Introduction: Coronary artery disease (CAD) is a life-threatening cardiac condition with high morbidity and mortality worldwide. This systematic review article highlighted the therapeutic roles of mesenchymal stromal cells (MSCs)-derived exosomal microRNAs (exo-miRs) in preclinical models of CAD.
    Methods: A comprehensive search was conducted on PubMed, Web of Science, Scopus, and Google Scholar to identify relevant publications until 04 Apr 2025. The literature review focuses on the origin of MSCs, the technique employed for exosome extraction and identification, the route and frequency of exosomal administration, the mechanisms through which exo-miRs regulate paracrine activity, and their impact on cardiac outcome.
    Results: After meticulous evaluation, fifty-six studies were deemed eligible for inclusion in this systematic review. Bone marrow-derived MSCs were the most commonly utilized cell type in the preclinical studies. The majority of studies employed the ultracentrifugation method for exosome isolation from MSCs. The administration of exosomes was primarily achieved through a single intramyocardial injection, utilizing a wide range of exosome concentrations (ranging from 0.02-400 μg/μL).
    Conclusion: The included studies predominantly have reported the anti-inflammatory, anti-apoptotic, angiogenic, antifibrotic, and reparative effects of MSC-exo-miRs, especially under hypoxic conditions. These findings support the capacity of MSC-exo-miRs to regulate the immune system and facilitate cardiac recovery following an injury.
    Keywords:  Coronary heart disease; Exosomes; Ischemic heart disease; Mesenchymal stem cells; Myocardial infarction; microRNA
    DOI:  https://doi.org/10.34172/bi.30989
  7. Int J Oncol. 2025 Dec;pii: 101. [Epub ahead of print]67(6):
    Exosomal microRNAs: A new role in the diagnosis and treatment of lung cancer metastases (Review).
    Xin Li, Jian Wang, Weipeng Ge, Xiinbo Chen.
      Lung cancer (LC) is a lethal malignancy that can pose a serious risk to a patient's health. Tumor metastasis is associated with a shorter survival and poor therapeutic outcomes. Epithelial‑mesenchymal transition, cell proliferation and angiogenesis are the key drivers of metastasis, which accounts for cancer malignancy. Exosomal microRNAs (miRNAs) are miRNAs packed and released in exosomes. Exosomal miRNAs promote the metastasis of LC. As the amount and type of exosomal miRNAs are disrupted in pathological situations, they may serve as markers for the diagnosis and treatment of LC. The present review summarizes the effects and underlying mechanisms of exosomal miRNAs in LC metastasis. It also provides an overview of the potential of exosomal miRNAs as diagnostic indicators and therapeutic targets for LC metastasis, highlighting novel avenues for future tailored therapies.
    Keywords:  exosomal; lung cancer; metastasis; microRNAs
    DOI:  https://doi.org/10.3892/ijo.2025.5807
  8. Brain Behav Immun Health. 2025 Nov;49 101113
    The roles of exosomes in the pathogenesis and treatment of coronary heart disease with depression and/or anxiety.
    Jiecheng Huang, Ying Piao, Xin Jiang, Jingjin Liu.
      Coronary heart disease (CHD) patients have been found to also possess high anxiety and depression rates, which have been considered as significant risk factors for the disease. One possible underlying biological mechanism behind anxiety/depression being associated with CHD may be exosomes, extracellular vesicles produced by cells throughout the body. These exosomes contain various proteins and miRNAs that could exert a variety of physiological and pathological effects. However, the precise role they play in CHD with anxiety/depression has still not been fully elucidated. In this review, we summarized the current research on exosome involvement in the pathogenesis of CHD with anxiety/depression, particularly focusing on inflammatory responses, neuroendocrine signaling, sympathetic nervous system (SNS) regulation, platelet activation, and endothelial injury. In particular, for inflammatory responses, exosomes have been associated with increased pro-inflammatory cytokine release, such as interleukin (IL)-1β, while for neuroendocrine signaling, the miRNAs miR-135a-5p and miR-320a have been implicated in increasing glucocorticoid signaling. As for SNS regulation, exosome miRNAs are involved in downregulating Nrf2, leading to increased sympathetic nerve excitation, while inhibiting exosome production counteracts platelet activation, in turn lowering thrombosis risk for CHD. Endothelial dysfunction could be promoted by exosomes carrying miR-155. On the other hand, exosome contents exert beneficial effects that could be used for treatment strategies, such as miR-1246 alleviating hypoxia-induced myocardial tissue damage, as well as miR-188-3p lowering nigrostriatal autophagy. Overall, identifying the roles that exosomes play in CHD with concurrent anxiety/depression pathogenesis, as well as potential alleviation, may be greatly beneficial for formulating effective treatment strategies.
    Keywords:  Anxiety; Coronary heart disease; Depression; Exosomes; Pathogenesis; Treatment
    DOI:  https://doi.org/10.1016/j.bbih.2025.101113
  9. J Nanobiotechnology. 2025 Oct 10. 23(1): 643
    Microneedles combining delivery of hUMSC-derived exosomes and EGCG mitigate UV-induced skin damage.
    Chenhui He, Zeqian Wang, Zhaoting Jiang, Yuqi Zhou, Xiaoqi Chen, Jia Zhang, Bo Wang, Qi Wang, Tong Wu, Chunying Li, Zhe Jian.
      Exposure to ultraviolet (UV) radiation compromises both the aesthetic and functional properties of the skin, accelerates aging, increases the risk of skin cancer, and significantly impairs quality of life. Exosomes derived from human umbilical cord mesenchymal stem cells (hUMSC-Exo) and natural compounds such as epigallocatechin gallate (EGCG) show great therapeutic potential for UV-induced skin damage. However, their efficacy is often limited by poor stability, low bioavailability, and inefficient skin penetration. In this study, we show that hUMSC-Exo and EGCG act synergistically to reduce oxidative stress and exert potent anti-inflammatory effects. By incorporating these agents into a microneedle-based delivery system, we achieved efficient transdermal co-delivery, which significantly enhanced the repair of UV-induced skin injury. The treatment markedly attenuated inflammatory responses, reduced DNA damage, and promoted tissue regeneration. These findings suggest that hUMSC-Exo/EGCG-loaded microneedles provide a simple yet effective strategy for treating UV-induced skin damage and aging, with potential applicability to a broader range of inflammatory skin conditions.
    Keywords:  EGCG; Exosomes; Microneedles; Skin photodamage
    DOI:  https://doi.org/10.1186/s12951-025-03735-x
  10. Biomed Pharmacother. 2025 Oct 04. pii: S0753-3322(25)00810-8. [Epub ahead of print]192 118616
    Therapeutic effect of neural induced-stem cell-derived exosomes by regulating ERK/p38/NF-κB in traumatic brain injury.
    Dohee Kim, Jinsu Hwang, Eunjae Jang, Hyong-Ho Cho, Byeong C Kim, Han-Seong Jeong, Sujeong Jang.
      Traumatic brain injury (TBI) can occur because of sudden external forces, such as falls or accidents, and it can cause immediate and long-term damage to the central nervous system. In this study, the therapeutic effects of neural-induced human adipose tissue-derived stem cell-derived exosomes (NI-Exo) on TBI were investigated. Exosomes were isolated and characterized through nanoparticle tracking analysis, cryo-transmission electron microscopy, and western blotting analysis. The therapeutic effects of NI-Exo were assessed in LPS-stimulated human microglial cells and TBI mice via behavioral tests (rotarod, elevated body swing, and cylinder tests), qPCR, western blotting analysis, and immunostaining. In the in vitro study, NI-Exo significantly downregulated pro-inflammatory cytokines (IL-6, IL-1β, and TNF-α) and upregulated anti-inflammatory cytokines (IL-4 and IL-10). In the in vivo study, NI-Exo (1 × 10⁴ or 1 × 10⁵ particles/mL) was administered intracerebroventricularly 1 h post-surgery to verify the effect on the in vivo model. In the TBI mouse model, NI-Exo improved asymmetric behaviors and reduced tissue disruption and cell loss. The protein levels of pro-apoptosis (p53, ROCK1, and Bax) decreased and those of anti-apoptosis (Mcl-1) increased in the NI-Exo group compared with those in the TBI group. Mechanistic investigations revealed that NI-Exo inhibited ERK and p38 phosphorylation, highlighting its role in mitigating neuroinflammation via the ERK/p38/NF-κB signaling pathway. Therefore, NI-Exo promoted anti-inflammation in human microglia and TBI mouse models; it also improved anti-apoptosis in TBI models, thereby offering a promising therapeutic potential for TBI treatment through the ERK/p38/NF-κB pathway.
    Keywords:  Apoptosis; ERK; Exosome; Inflammation; NF-κB; Traumatic brain injury; p38
    DOI:  https://doi.org/10.1016/j.biopha.2025.118616
  11. ACS Infect Dis. 2025 Oct 09.
    Platelet-Derived Transforming Growth Factor-β1: A New Hope for Cerebral Malaria Treatment.
    Shuangchun Liu, Bingjing Guo, Liguo Song, Guang Chen, Tao Zhang, Yunting Du.
      Cerebral malaria (CM), a fatal neurological complication arising from Plasmodium falciparum (P. falciparum) infection, remains a significant global health challenge due to the inadequacy of current drugs and vaccines. Consequently, novel therapeutic strategies for CM are urgently needed. Recent research identifies platelets as pivotal in CM pathogenesis, significantly contributing to immunopathological damage and vascular blockage. Platelet-derived transforming growth factor (TGF)-β1 induces apoptosis in endothelial cells, fostering microangiopathy and potentially compromising blood-brain barrier integrity, thus provoking brain edema and inflammation. Notably, TGF-β1 concentrations vary markedly between systemic and local levels, with reduced TGF-β1 levels in mouse/human tissue and peripheral circulation correlating with CM severity. The primary regulatory mechanism involves isolated platelets interacting with infected red blood cells and brain endothelium, elevating local TGF-β1 production, and possibly harming brain endothelial cells. Future CM prevention or treatment strategies should focus on targeting TGF-β1, with an emphasis on brain-targeted drug delivery methods. Exosomes, as natural drug carriers, are extensively utilized for brain-specific delivery. Exosomes loaded with TGF-β1 antibodies, which were surface to enhancing brain-targeting ability, offer a promising therapeutic approach for CM.
    Keywords:  TGF-β1; cerebral malaria; exosome loading; platelet; treatment
    DOI:  https://doi.org/10.1021/acsinfecdis.5c00710
  12. Int Arch Allergy Immunol. 2025 Oct 08. 1-17
    RNA-editing enzyme ADAR1 attenuates rheumatoid arthritis via regulating fibroblast-like synoviocytes-derived exosomal circFTO.
    Yuxuan Fang, Nan Xu, Jiacheng Shen, Hongyi Chen, Yimin Ding, Guoqing Li.
      Rheumatoid arthritis (RA) is a chronic debilitating autoimmune disorder and a predominant cause of potentially treatable functional disability. Adenosine deaminase acting on RNA 1 (ADAR1), as an RNA-editing enzyme, can regulate circular RNAs (circRNAs) and fibroblast-like synoviocytes (FLSs)-derived exosomal circFTO has been proposed as a contributor to RA. This study was dedicated to elaborate the role of ADAR1 in RA and the association between ADAR1 and circFTO. RT-qPCR examined circFTO, fat mass and obesity-associated protein (FTO), DExH-box helicase 9 (DHX9), ADAR1 and Quaking (QKI) expressions in RA-FLSs and human fibroblast-like synoviocytes (HFLSs), and circFTO expression in RA-FLSs- or HFLSs-derived exosomes. In severe combined immunodeficiency (SCID) mice engrafted with human cartilage and rheumatoid synovium tissue (SCID-HuRAg), the in vivo imaging technique was adopted to track the distribution and migration of RA-FLSs and HFLSs. H&E staining and Safranin-O staining measured the severity of RA and engrafted cartilage degradation. Immunohistochemistry assessed the expression of inflammation-, anabolic- and catabolic-related genes. Also, RT-qPCR examined the expressions of circFTO, miR-548a-3p, heterogeneous nuclear ribonucleoprotein A2B1 (hnRNPA2B1), anabolic- and catabolic-related genes. ADAR1 was lowly expressed in RA-FLSs and ADAR1 silencing reduced circFTO expression in RA-FLSs-derived exosomes. In vivo, RA-FLSs were widely distributed and the migration capability was enhanced compared with HFLSs. ADAR1 overexpression efficiently decreased arthritis severity, attenuated cartilage degradation and inflammatory response in SCID-HuRAg mice injected with RA-FLSs. Besides, ADAR1 could decrease circFTO and hnRNPA2B1 expressions while elevating miR-548a-3p expression, particularly in SCID-HuRAg mice injected with RA-FLSs. To summarize, our findings identify ADAR1 as a potential treatment target for RA at least partially via regulating circFTO.
    DOI:  https://doi.org/10.1159/000547802
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