bims-engexo 2025-08-31 papers

bims-engexo

Biomed News

on Engineered exosomes

Issue of 2025–08–31
eight papers selected by
Ravindran Jaganathan, Universiti Kuala Lumpur

Engineered exosomes: a promising design platform for overcoming cancer therapy resistance.
GLP-2-carrying exosomes alleviate osteoporosis by upregulating miR-378a-3p to inhibit osteoclastic differentiation and NF-κB-MAPK pathway.
Study on the Mechanism of Bone Marrow Stem Cell-Derived Exosome miR-30a/DLL4 Acting on Traumatic Brain Injury Angiogenesis.
Exosomal miR-214-3p reprograms BMSC fate: A novel intercellular mechanism linking vascular insufficiency to impaired bone regeneration in nontraumatic ONFH.
Immunomodulatory and Regenerative Functions of MSC-Derived Exosomes in Bone Repair.
Basophil-derived exosomes exacerbate systemic lupus erythematosus by regulating B-cell proliferation via miR-24550.
Hypoxia-induced exosomal circNRIP1 activates cancer-associated fibroblasts to promote esophageal squamous cell carcinoma migration and invasion.
Conductive Microneedles Loaded With Polyphenol-Engineered Exosomes Reshape Diabetic Neurovascular Niches for Chronic Wound Healing.

Front Cell Dev Biol. 2025 ;13 1608480

Engineered exosomes: a promising design platform for overcoming cancer therapy resistance.

Peng Zhang, Kai Chen, Weifeng Liu, Xiaoying Niu, Xin Wang, Jiaqiang Wang, Weitao Yao, Xiaodong Tang, Wen Tian.

  Therapeutic resistance is a formidable barrier in cancer treatment, necessitating innovative solutions to enhance drug efficacy. Exosomes, with their unparalleled biocompatibility, low immunogenicity, and robust cargo protection, have emerged as groundbreaking nanocarriers. This review unveils the transformative potential of exosomes in overcoming drug resistance - encompassing chemotherapy, targeted therapy, and immunotherapy - in a wide spectrum of tumors. Through advanced genetic and non-genetic modifications, exosomes can dramatically enhance drug targeting and cytotoxicity, offering unprecedented precision in treatment. We explore state-of-the-art exosome engineering techniques, their revolutionary applications in clinical trials, and their promise as the next Frontier in therapeutic innovation. This comprehensive review aims to capture the cutting-edge developments and future directions of exosome-based therapies, positioning them as a cornerstone of next-generation oncology.

Keywords:  chemotherapy resistance; engineered exosome; immunotherapy resistance; precise treatment; targeted therapy resistance

DOI:  https://doi.org/10.3389/fcell.2025.1608480
J Orthop Surg Res. 2025 Aug 25. 20(1): 797

GLP-2-carrying exosomes alleviate osteoporosis by upregulating miR-378a-3p to inhibit osteoclastic differentiation and NF-κB-MAPK pathway.

Jiping Shen, Kefen Wu, Yi Lu, Kan Xu, Yanling Huang, Yu Hu.

   BACKGROUND: Osteoporosis, characterized by excessive osteoclast activity, remains a major health challenge. This study investigated the therapeutic potential of exosomes derived from glucagon-like peptide-2 (GLP-2)-overexpressing macrophages in osteoporosis, with specific focus on miR-378a-3p-mediated regulation of osteoclastogenesis and inflammatory signaling pathways.
METHODS: GLP-2 was overexpressed in mouse RAW264.7 cells. Exosomes were extracted and characterized. In vitro, effects on osteoclast differentiation were assessed using Cell Counting Kit-8, tartrate-resistant acid phosphatase staining, and quantitative real-time polymerase chain reaction. Differentially expressed miRNAs were screened via bioinformatics analysis. In vivo, an osteoporosis rat model was induced by bilateral ovariectomy. Histopathological evaluation of femoral tissue was performed via Hematoxylin-Eosin and tartrate resistant acid phosphatase staining. Bone microarchitecture, inflammatory cytokines, and signaling pathways were evaluated using micro-CT, enzyme-linked immunosorbent assay, and western blotting. Moreover, miR-378a-3p antagonist was applied to investigate the role of miR-378a-3p in osteoporosis.
RESULTS: GLP-2-carrying exosomes inhibited osteoclast differentiation in vitro and improved bone microarchitecture in vivo. Bioinformatics analysis identified miR-378a-3p as a hub miRNA and miR-378a-3p was downregulated in osteoporosis. In vivo, GLP-2-carrying exosomes promoted miR-378a-3p level and inhibited osteoclast differentiation. MiR-378a-3p mimics inhibited the NF-κB/MAPK signaling, and the direct binding specificity between miR-378a-3p and TRAF6 was validated via dual-luciferase reporter assay. Mechanistically, GLP-2-carrying exosomes enhanced bone parameters, suppressed inflammation and NF-κB/MAPK signaling pathway, which were reversed by miR-378a-3p antagonist.
CONCLUSION: GLP-2-carrying exosomes showed promise in treating osteoporosis by inhibiting osteoclast differentiation and modulating NF-κB/MAPK pathways via miR-378a-3p regulation. This novel axis presents a promising dual-targeted strategy for osteoporosis treatment, with engineered exosomes offering significant translational potential for bone regenerative therapy.

Keywords:  Exosome; GLP-2; NF-κB/MAPK pathway; Osteoporosis; miR-378a-3p

DOI:  https://doi.org/10.1186/s13018-025-06119-x
J Craniofac Surg. 2025 Jul-Aug 01;36(5):36(5): 1849-1856

Study on the Mechanism of Bone Marrow Stem Cell-Derived Exosome miR-30a/DLL4 Acting on Traumatic Brain Injury Angiogenesis.

Wei Hu, Jiang Zhou, Rui-Hai Zhang, Xiao-Ming Hu.

   OBJECTIVE: To explore the effects of bone marrow stem cell (BMSC)-derived exosome miR-30a/DLL4 expression on angiogenesis following traumatic brain injury (TBI), which may provide a novel therapeutic strategy for postoperative TBI recovery.
METHODS: A rat TBI model was established using the free-fall method, and exosomes from different sources were injected into the brain. Rats were divided into sham-operated, TBI model, TBI+inhibitor NC-Exo, TBI+miR-30a-inhibitor-Exo, TBI+OE NC-Exo, and TBI+DLL4-OE-Exo groups. Neurological function was assessed using mNSS and water maze tests. H&E staining, immunohistochemistry (CD31, CD34, GFAP, NSE, DLL4, VEGF), and qPCR (miR-30a-5p, DLL4, VEGF mRNA) were performed to evaluate angiogenesis and neurorepair.
RESULTS: Hematoxylin and eosin staining confirmed successful TBI modeling, with reduced neurons and pathologic changes in the injury foci. Exosomes with low miR-30a-5p and high DLL4 expression alleviated TBI pathology and improved neurological function. qPCR showed that miR-30a-5p downregulation and DLL4 upregulation reduced VEGFA expression. Immunohistochemistry revealed low CD31, CD44, and VEGFA, and high DLL4, GFAP, and NSE in the TBI model. BMSC exosome treatment upregulated vascular markers (CD31, CD44, and VEGFA) and downregulated injury markers (GFAP and NSE), effects reversed by miR-30a-5p inhibition and DLL4 overexpression.
CONCLUSION: Bone marrow stem cell exosomes promote post-TBI angiogenesis and nerve function recovery, partially through the regulation of miR-30a-5p and DLL4 expression. These findings suggest that BMSC-derived exosomes may offer a novel therapeutic strategy for TBI and craniofacial trauma. For surgeons, this study provides a preclinical foundation for developing exosome-based intraoperative adjuvants to enhance vascularization in trauma sites, thereby improving graft survival in reconstructive surgery and reducing postoperative complications such as ischemia-reperfusion injury.

Keywords:  Angiogenesis; BMSC-Exo; DLL4; TBI; miR-30a-5p; nerve injury

DOI:  https://doi.org/10.1097/SCS.0000000000011580
Mol Immunol. 2025 Aug 22. pii: S0161-5890(25)00208-1. [Epub ahead of print]186 147-160

Exosomal miR-214-3p reprograms BMSC fate: A novel intercellular mechanism linking vascular insufficiency to impaired bone regeneration in nontraumatic ONFH.

Shifan Lin, Jian Xia, Jian Ding, Jie Wan.

   BACKGROUND: Nontraumatic osteonecrosis of the femoral head (NONFH) is a debilitating bone disorder of unclear etiology, characterized by impaired bone regeneration and reduced vascularization. However, the influence of NONFH-derived exosomes on bone marrow stromal cell (BMSC) differentiation and angiogenesis remains poorly understood.
METHODS: Exosomes were isolated from femoral head tissues of NONFH patients and fracture controls (femoral neck fractures). Their characteristics were confirmed by transmission electron microscopy (TEM), nanoparticle tracking analysis (NTA), and Western blot. BMSCs were treated with different exosomes (control exosomes, NONFH exosomes, or NONFH exosomes + miR-214-3p inhibitor), and osteogenic/adipogenic differentiation was assessed by alkaline phosphatase activity, calcium deposition, osteogenic/adipogenic marker expression, and Oil Red O staining. Human umbilical vein endothelial cells (HUVECs) were similarly treated, and angiogenesis was evaluated via tube formation assays. In vivo, exosomes were injected into rats, and femoral changes were analyzed by Western blot, hematoxylin-eosin (HE) staining, and immunohistochemistry.
RESULTS: Exosomes from both groups exhibited typical morphology, size, and marker expression. NONFH exosomes suppressed BMSC osteogenesis, enhanced adipogenesis, and impaired HUVEC angiogenesis, with miR-214-3p as a critical mediator. Inhibiting miR-214-3p partially restored osteogenic and angiogenic capacities. In rats, NONFH exosomes reduced osteogenic protein expression, expanded marrow cavities, and disrupted trabecular bone structure, while miR-214-3p inhibition ameliorated these effects.
CONCLUSION: NONFH-derived exosomes contribute to disease progression by delivering miR-214-3p, which inhibits BMSC osteogenesis and HUVEC angiogenesis. Targeting this pathway may offer novel therapeutic strategies for NONFH.

Keywords:  Angiogenesis; Bone Marrow Stromal Cells; Exosomes; MiR-214–3p; Nontraumatic Osteonecrosis of the Femoral Head; Osteogenic Differentiation

DOI:  https://doi.org/10.1016/j.molimm.2025.08.014
Bioengineering (Basel). 2025 Aug 05. pii: 844. [Epub ahead of print]12(8):

Immunomodulatory and Regenerative Functions of MSC-Derived Exosomes in Bone Repair.

Manorathna Arun, Sheeja Rajasingh, Parani Madasamy, Johnson Rajasingh.

  Bone integrity is maintained through continuous remodeling, orchestrated by the coordinated actions of osteocytes, osteoblasts, and osteoclasts. Once considered passive bystanders, osteocytes are now recognized as central regulators of this process, mediating biochemical signaling and mechanotransduction. Malfunctioning osteocytes contribute to serious skeletal disorders such as osteoporosis. Mesenchymal stromal cells (MSCs), multipotent stem cells capable of differentiating into osteoblasts, have emerged as promising agents for bone regeneration, primarily through the paracrine effects of their secreted exosomes. MSC-derived exosomes are nanoscale vesicles enriched with proteins, lipids, and nucleic acids that promote intercellular communication, osteoblast proliferation and differentiation, and angiogenesis. Notably, they deliver osteoinductive microRNAs (miRNAs) that influence osteogenic markers and support bone tissue repair. In vivo investigations validate their capacity to enhance bone regeneration, increase bone volume, and improve biomechanical strength. Additionally, MSC-derived exosomes regulate the immune response, creating pro-osteogenic and pro-angiogenic factors, boosting their therapeutic efficacy. Due to their cell-free characteristics, MSC-derived exosomes offer benefits such as diminished immunogenicity and minimal risk of off-target effects. These properties position them as promising and innovative approaches for bone regeneration, integrating immunomodulatory effects with tissue-specific regenerative capabilities.

Keywords:  bone regeneration; exosomes; immunomodulation; mesenchymal stromal cells; osteocytes

DOI:  https://doi.org/10.3390/bioengineering12080844
BMC Med. 2025 Aug 22. 23(1): 490

Basophil-derived exosomes exacerbate systemic lupus erythematosus by regulating B-cell proliferation via miR-24550.

Jiaxuan Chen, Shuzhen Liao, Jiaqi Lun, Xing Lu, Bitang Huang, Xiaoxian Liu, Xiaowei Xu, Lawei Yang, Fengbiao Guo, Liuyong You, Haiyan Xiao, Hua-Feng Liu, Qingjun Pan.

   BACKGROUND: Systemic lupus erythematosus (SLE) is a complex autoimmune disease where B-cell proliferation and activation play a pivotal role in pathogenesis. While the role of basophils in SLE is recognized, the impact of basophil-derived exosomes on B-cell proliferation and activation has not been thoroughly investigated.
METHODS: Exosomes from human basophils in both resting and activated states were isolated and characterized. These exosomes were then co-cultured with B cells to assess their effects on B-cell survival and proliferation. To investigate the in vivo roles, a Pristane-induced lupus model in Mcpt8flox/flox CAGGCre-ERTM mice was utilized. The Pristane-Mcpt8flox/flox, CAGGCre-ERTM mice were analyzed for basophil-derived exosome accumulation in the spleen and kidneys, and the effects on immune cell proliferation and plasma cell-plasmablast balance were assessed. Transcriptomic analysis was conducted on basophil-derived exosomes to identify key non-coding RNAs. Lupus mice were humanized by transplanting peripheral blood mononuclear cells (PBMCs) from patients with SLE into immunodeficient mice to evaluate the effects of intervening miR-24550 in B cells.
RESULTS: Activated basophil-derived exosomes were found to enhance B-cell survival and proliferation in patients with SLE. In the lupus mouse model, basophil-derived exosomes accumulated primarily in the spleen and kidneys, inducing excessive immune cell proliferation and disrupting the plasma cell-plasmablast balance, which worsened kidney damage. Transcriptomic analysis revealed key non-coding RNAs within basophil-derived exosomes. Activated basophil-derived exosomes were internalized by B cells, releasing miR-24550, which promoted B-cell proliferation. In humanized SLE mice, inhibiting miR-24550 in B cells reduced immune hyperactivation and improved renal function, similar to the effects of inhibiting basophil-derived exosomes release in Pristane-Mcpt8flox/flox, CAGGCre-ERTM mice. Ultimately, basophil-derived exosomal miR-24550 promotes B-cell proliferation and activation by targeting Krüppel-like factor 5 (KLF5), which exacerbates SLE progression.
CONCLUSIONS: Basophil-derived exosomal miR-24550 promotes B-cell proliferation and activation by targeting KLF5, thereby exacerbating SLE progression. This study presents a novel strategy for SLE prevention and treatment.

Keywords:  B cells; Basophils; Exosomes; Systemic lupus erythematosus; miR-24550

DOI:  https://doi.org/10.1186/s12916-025-04324-3
BMC Gastroenterol. 2025 Aug 20. 25(1): 605

Hypoxia-induced exosomal circNRIP1 activates cancer-associated fibroblasts to promote esophageal squamous cell carcinoma migration and invasion.

Guan'en Qiao, Changjuan Li, Meng Wang, Wenjuan Zhang, Junjie Shi, Bing Meng, Lixia Zhang, Ruiqing Zhang, Huihui Qi, Shuanli Xin.

  Esophageal squamous cell carcinoma (ESCC) is characterized by a complex tumor microenvironment (TME). Cancer-associated fibroblasts (CAFs) play a crucial role in the TME that facilitate tumor progression via interactions with cancer cells. However, the mechanisms underlying the activation of CAFs in TME remain largely unknown. Here, we characterized the exosomes derived from normoxic and hypoxic ESCC cells using electron microscopy and western blot. The impact of exosomes on CAF activation and the motility of ESCC cells was examined in vitro. The molecular complex involving circNRIP1 was explored using RNA pull-down. We demonstrated that exosomes derived from ESCC cells, including KYSE-150 and TE-10 cells, exhibited a significantly increase in secretion under hypoxic conditions. These hypoxic exosomes were internalized by fibroblasts and further promoted the transformation of normal fibroblasts into CAFs, as evidenced by enhanced migration and secretion of pro-inflammatory cytokines. circNRIP1 was enriched in hypoxic exosomes, and its absence abolished the effect of hypoxic exosomes to activate CAFs. Furthermore, the CAFs activated by exosomal circNRIP1 further promoted the migration and invasion of ESCC cells. Mechanistically, circNRIP1 bound to the N1-methyladenosine (m1A) methyltransferase TRMT6 and activated CAFs in a TRMT6-dependent manner. This study revealed the role of hypoxia-induced exosomal circNRIP1 in the activation of CAFs, which contributes to ESCC development. These findings shed light on the mechanisms of the CAF activation in ESCC, positioning hypoxia-induced exosomal circNRIP1 as a potential molecular target for ESCC.

Keywords:  Cancer-associated fibroblast; CircNRIP1; Esophageal squamous cell carcinoma; Exosome; Hypoxia

DOI:  https://doi.org/10.1186/s12876-025-03978-w
Adv Sci (Weinh). 2025 Aug 26. e07974

Conductive Microneedles Loaded With Polyphenol-Engineered Exosomes Reshape Diabetic Neurovascular Niches for Chronic Wound Healing.

Di Liu, Jingxian Gao, Xueling Wu, Xinxin Hao, Wenxiu Hu, Lu Han.

  Diabetic wound healing remains a major clinical challenge due to the accumulation of advanced glycation end products (AGEs), reactive oxygen species (ROS), and proinflammatory cytokines under hyperglycemic conditions, which collectively impair neurovascular regeneration. Here, a biological-electrical therapeutic platform is reported by synergizing polyphenol-engineered Saccharina japonica exosomes (CA@Exos)-derived biological signals with electroconductive microneedles (pCNTs-ASA MNs)-delivered electrical cues, achieving a dual-pathway to reshape neurovascular niches during the diabetic wound healing process. CA@Exos serve as bioactive cargo to suppress AGE formation, scavenge ROS, and reverse the inflammatory microenvironment, while their intrinsic bioactivities in modulating angiogenesis and neurotrophic signaling enhanced Schwann cell-vascular endothelial cell crosstalk. Concurrently, the conductive pCNTs-ASA MNs functioned as spatiotemporal bioelectric scaffolds, enhancing exosome uptake and amplifying endogenous wound currents by transmitting exogenous electrical stimulation. This dual-modality strategy synergistically promotes angiogenesis, neural regeneration, and re-epithelialization, achieving full-thickness wound closure in diabetic rats. This work pioneers the therapeutic potential of plant-derived exosomes with conductive MNs-mediated biophysical stimulation, offering a promising therapeutic strategy to disrupt the pathological feedback loop of hyperglycemic microenvironment for diabetic wound healing. The combined strategy, supported by a favorable biosafety profile and high adaptability, demonstrates a bright prospect for clinical translation, offering new hope for patients with chronic diabetic wounds.

Keywords:  conductive microneedles; diabetic wound healing; exosomes; plant polyphenol

DOI:  https://doi.org/10.1002/advs.202507974