bims-engexo 2025-08-24 papers

bims-engexo

Biomed News

on Engineered exosomes

Issue of 2025–08–24
seven papers selected by
Ravindran Jaganathan, Universiti Kuala Lumpur

Engineered Extracellular Vesicles in Arthritic Diseases: Therapeutic Applications & Challenges.
Exosomes from small intestinal epithelium mediate cardiac fibrosis during aging.
Advances in the Role of Stem Cell-Derived Exosomes in Diabetic Foot Wound Healing.
[Research advances of exosomal micrornas in regulating the pathogenesis of acute lung injury/acute respiratory distress syndrome].
Islet Tissue Macrophages in Immunity Homeostasis and Type 1 Diabetes.
Comparisons of miRNA profiles of exosomes derived from human iPSCs, ADSCs, and BMSCs and effects on chondrocyte function.
The Diagnosis and Prognosis Value of Exosomal MascRNA in Patients with Acute Coronary Syndrome.

Wiley Interdiscip Rev Nanomed Nanobiotechnol. 2025 Jul-Aug;17(4):17(4): e70031

Engineered Extracellular Vesicles in Arthritic Diseases: Therapeutic Applications & Challenges.

Seif Ehab, Ola A Gaser, Atif Abdulwahab A Oyouni, Nader Kameli, Faisal Alzahrani, Ahmed Abdal Dayem.

  Arthritic diseases are a significant global health challenge, highlighting the urgent need for innovative therapeutic strategies. Extracellular vesicles (EVs) have emerged as promising candidates for treating various intractable diseases. This review explores the therapeutic potential of engineered EVs in joint diseases, particularly in comparison to their parental stem cells. Recent research underscores the efficacy of EVs in treating joint diseases, especially Osteoarthritis (OA). We discuss EV engineering strategies aimed at overcoming the limitations of natural EVs. Data from preclinical trials, clinical studies, and in vitro and in vivo reports are analyzed to evaluate the effectiveness of EVs in treating joint conditions. In addition to their role in intercellular communication, EVs influence various biological processes crucial for bone remodeling, cartilage regeneration, immunomodulation, and inflammation control. EVs are rich in vital biomolecules such as proteins, microRNAs (miRNA), lipids, and nucleic acids, which enhance their therapeutic potential compared to parental stem cells. This understanding is key to developing targeted and effective engineered EVs for OA and other joint diseases. A comprehensive grasp of EV engineering and underlying mechanisms will pave the way for novel and efficient therapies for arthritic diseases and related conditions. This article is categorized under: Implantable Materials and Surgical Technologies > Nanotechnology in Tissue Repair and Replacement Nanotechnology Approaches to Biology > Cells at the Nanoscale Biology-Inspired Nanomaterials > Peptide-Based Structures.

Keywords:  arthritic diseases; cell free therapy; delivery; engineering; extracellular vesicles; stem cells

DOI:  https://doi.org/10.1002/wnan.70031
J Gerontol A Biol Sci Med Sci. 2025 Aug 18. pii: glaf183. [Epub ahead of print]

Exosomes from small intestinal epithelium mediate cardiac fibrosis during aging.

Yijun He, Xuanbei Lu, Sisi Pang, Fan Xia, Yifan Lv, Jing Yu, Guoxian Ding, Yunlu Sheng.

  Senescent cardiac fibroblasts (CFs), which are activated and acquire a pro-fibrotic phenotype, exacerbate age-related interstitial fibrosis and cardiac dysfunction by unclear mechanisms. Traditionally regarded as a central organ involved in regulating aging, the small intestine (SI) communicates with remote organs. However, the mechanisms underlying its role in CFs senescence remain undefined. We aimed to clarify whether the SI epithelium-derived exosomes (SI-exos) and their contained microRNAs could regulate CFs senescence and participate in deteriorating cardiac fibrosis during aging. Systemic administration of aged SI-exos exerted deleterious effects on the hearts of young recipient mice, as evidenced by exacerbated cardiac aging, inflammation, fibrosis, and the resulting poorer cardiac function. In vitro studies revealed that aged SI-exos could induce the activation and senescence of young CFs, while treatment with young SI-exos mitigated the activation and senescence of aged CFs. Mechanistic investigation identified that miR-223-3p was a common molecule significantly increased both in aged SI-exos and aged serum-exos. Incubation of young CFs with miR-223-3p mimics exacerbated cellular activation and senescence by cooperatively suppressing target genes: RASA1 and KLF15. In contrast, miR-223-3p inhibitor could rescue D-gal-induced CFs activation and senescence. Over-expression of RASA1 or KLF15 significantly rescued miR-223-3p-induced CFs activation and senescence. Summarily, our findings demonstrate for the first time that miR-223-3p enrichment in aged SI-exos, and its suppression of RASA1 and KLF15 in CFs, is a novel potential mechanism exacerbating cardiac aging and fibrosis. Targeting miR-223-3p mediated pathological communication between the aged SI epithelium and CFs might be an effective strategy for cardioprotection during aging.

Keywords:  aging; cardiac fibrosis; exosomes; small intestinal epithelium

DOI:  https://doi.org/10.1093/gerona/glaf183
Diabetes Metab Syndr Obes. 2025 ;18 2767-2781

Advances in the Role of Stem Cell-Derived Exosomes in Diabetic Foot Wound Healing.

Junbo Wang, Yu-Jie Liang, Xiaohua Pan.

  Chronic hyperglycemia over a long period can lead to diabetes-related complications, of which diabetic foot ulcers continue to have a huge economic and social impact worldwide. Mesenchymal stem cell-derived exosomes (MSC-Exos) have demonstrated positive efficacy in the preclinical research and clinical trial phases of diabetic foot ulcer (DFU) treatment. In this review, we provide a brief overview of the properties of MSC-derived exosomes and their biological functions, summarize the therapeutic efficacy of Exos in the treatment of diabetic foot ulcers and its mechanism of action, and discuss innovative technologies including hydrogel scaffolds and 3D bioprinting to enhance the effectiveness of MSC - Exos in the treatment of diabetic foot ulcers. This paper also explores the application of innovative technologies such as hydrogel scaffolds and 3D bioprinting in enhancing the efficacy of MSC-Exos in the treatment of diabetic foot ulcers and highlights the key challenges faced in translating these advanced technologies from the laboratory to the clinic.

Keywords:  chronic wounds; diabetic foot ulcers; stem cell-derived exosomes; tissue engineering; translational research

DOI:  https://doi.org/10.2147/DMSO.S521095
Zhonghua Wei Zhong Bing Ji Jiu Yi Xue. 2025 May;37(5): 494-498

[Research advances of exosomal micrornas in regulating the pathogenesis of acute lung injury/acute respiratory distress syndrome].

Lingshuang Chen, Jun Lyu, Xianming Zhang.

Acute lung injury/acute respiratory distress syndrome (ALI/ARDS) is a severe critical condition marked by rapid progression and high fatality. It results from direct/indirect lung-related or systemic triggers, leading to widespread injury of lung epithelial and endothelial cells. Its pathogenesis involves uncontrolled inflammation and breakdown of the lung's blood-air barrier due to leaky blood vessels and epithelial damage. Current management of ALI/ARDS remains primarily supportive, offering symptomatic relief but limited improvement in prognosis, necessitating deeper exploration of upstream pathogenic mechanisms to identify safer and more effective therapies. Exosomal microRNAs (miRNA), small extracellular vesicles (40-150 nm) containing non-coding single-stranded RNAs, regulate post-transcriptional cellular processes and participate in ALI/ARDS pathophysiology. Studies reveal that exosomes transport proteins, nucleic acids, and miRNAs to recipient cells, mediating intercellular communication. In ALI/ARDS models, exosomal miRNAs delivered to alveolar epithelial cells, endothelial cells, macrophages, and neutrophils critically modulate autophagy, pyroptosis, apoptosis, proliferation, inflammatory signaling, macrophage polarization, and neutrophil activation, either exacerbating or alleviating disease progression. Recent advances in engineering techniques have enhanced the therapeutic potential of exosomal miRNAs by overcoming limitations of natural exosomes. This review focuses on exosomal miRNA-mediated regulation of ALI/ARDS pathogenesis across key cell types, providing insights for novel therapeutic strategies.

DOI: https://doi.org/10.3760/cma.j.cn121430-20240802-00659
Clin Rev Allergy Immunol. 2025 Aug 18. 68(1): 82

Islet Tissue Macrophages in Immunity Homeostasis and Type 1 Diabetes.

Yan Wang, Zhaoran Wang, Wenya Diao, Tong Shi, Jiahe Xu, Tiantian Deng, Chaoying Wen, Jienan Gu, Tingting Deng, Sixuan Wang, Cheng Xiao.

  Islet macrophages are considered to be irreplaceable in maintaining the immune microenvironment homeostasis. The M1/M2 imbalance can trigger the initiation of islet autoimmunity and persists throughout the entire process of type 1 diabetes. The identification of macrophage transcriptional clusters and phenotypes by single-cell sequencing has facilitated in-depth studies on the role of macrophages in the pathogenesis of type 1 diabetes. Macrophages exert extensive endocrine and paracrine effects on the islets by secreting various bioactive chemicals, especially exosomes, which facilitate cell-cell communication. Resident islet macrophages directly influence the biological properties of islet tissue. Meanwhile, the interaction between macrophages and islet cells is bidirectional. Cell-cell interactions also closely govern the polarization and activity of macrophages. An imbalance in the transition from M2 to M1 macrophages may lead to inflammation and islet dysfunction. Here, we have discussed the latest research progress on macrophages in the islet immune microenvironment homeostasis, the mechanisms of interactions between macrophages and islet cells in type 1 diabetes, and analyzed the possible clinical consequences. Furthermore, we highlighted emerging technologies for non-invasive detection of macrophages and summarized how therapeutic targeting of macrophages may be beneficial for patients with type 1 diabetes.

Keywords:  Cell communication; Diabetes; Exosomes; Immunity homeostasis; Macrophage; β cell

DOI:  https://doi.org/10.1007/s12016-025-09084-9
Bone Joint Res. 2025 Aug 18. 14(8): 696-712

Comparisons of miRNA profiles of exosomes derived from human iPSCs, ADSCs, and BMSCs and effects on chondrocyte function.

Ling-Hua Chang, Shu-Chun Chuang, Shun-Cheng Wu, Yin-Chih Fu, Jhen-Wei Chen, Che-Wei Wu, Yi-Shan Lin, Cyong-Yue Liu, Yu-Hsuan Chung, Je-Ken Chang, Chung-Hwan Chen, Mei-Ling Ho.

Aims: This study aimed to identify and compare the microRNA (miRNA) profiles of exosomes derived from human induced pluripotent stem cells (iPSCs), bone marrow mesenchymal stem cells (BMSCs), and adipose tissue-derived stem cells (ADSCs) (hiPSC-Exos, hBMSC-Exos, and hADSC-Exos), and their functional effects on human articular chondrocytes (hACs).
Methods: hiPSC-Exos, hBMSC-Exos, and hADSC-Exos were collected from the appropriate cells cultured in 10% bovine exosome-depleted fetal bovine serum (de-Exo-FBS) for 48 hours. Next-generation sequencing (NGS) and bioinformatics were used to analyze the small RNA profiles of these exosomes. The biological functions of hACs were examined after a 12-day treatment with exosomes.
Results: hBMSC-Exos and hADSC-Exos had similar miRNA profiles but were largely different from hiPS-Exos. There were 17 highly expressed miRNAs in hiPSC-Exos, 13 miRNAs in hADSC-Exos, and 11 miRNAs in hBMSC-Exos. Among them, seven miRNAs overlapped between the hBMSC-Exos and hADSC-Exos, and only three of them (hsa-miR-16-5p, hsa-miR-25-3p, and hsa-miR-93-5p) overlapped among all three exosomes. The putative target genes of the three overlapping exosomal miRNAs, and high-scoring target genes, including MAN2A1, ZNFX1, PHF19, GPR137C, ENPP5, B3GALT2, FNIP1, PKD2, and FBXW7, were identified. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses revealed that these genes are involved in cell growth, bone ossification, and cartilage development/differentiation, possibly via the mitogen-activated protein kinase (MAPK) signalling pathway. Accordingly, we confirmed the biological effect on cartilage differentiation and found that hiPSC-Exos, hBMSC-Exos, and hADSC-Exos maintained hAC viability, prevented senescence, promoted the formation of a normal cartilage matrix (glycosaminoglycan and type II collagen), and downregulated fibrocartilage matrix (type I collagen) in normal hACs. Comparatively, hBMSC-Exos had the greatest effect on hAC function.
Conclusion: Bioinformatics revealed differences and possible mechanisms of action of exosomes derived from pluripotent hiPSCs, multipotent hADSCs, and multipotent hBMSCs, and these exosomes effectively suppressed cell senescence and promoted normal functional extracellular matrix formation in hACs. Further investigations of the different functions of exosomes from pluripotent-hiPSCs other than those from multipotent-hMSCs are needed.

DOI: https://doi.org/10.1302/2046-3758.148.BJR-2024-0267.R4
Int J Gen Med. 2025 ;18 4425-4436

The Diagnosis and Prognosis Value of Exosomal MascRNA in Patients with Acute Coronary Syndrome.

Jingyuan Hou, Ruiqiang Weng, Xiaodong Gu, Junli Zhao, Xia Li, Sudong Liu.

   Objective: MascRNA is involved in regulating the immune inflammatory response, but its role in acute coronary syndrome (ACS) remains unclear. This study aims to investigate the diagnostic and prognostic value of plasma exosomal mascRNA for ACS.
Methods: A total of 140 ACS patients and 50 patient with non-ACS were enrolled. Exosomes were isolated from plasma utilizing ultracentrifugation, and mascRNA expression in exosomes was quantified by qRT-PCR. Major adverse cardiovascular events (MACEs) occurring during the 1-year follow-up after stent implantation were recorded. The diagnostic value of exosomal mascRNA for ACS was evaluated utilizing receiver operating characteristic (ROC) analysis. The association between exosomal mascRNA level and MACEs was assessed by Kaplan-Meier survival analysis and Cox proportional-hazards regression.
Results: Exosomal mascRNA expression was significantly elevated in ACS patients, and positively correlated with Gensini score, white blood cells and age. Exosomal mascRNA demonstrated a diagnostic value for ACS (AUC: 0.763, 95% CI: 0.702-0.824). Combined detection of exosomal mascRNA with cTnI improved the diagnostic preformation for ACS (AUC: 0.866, 95% CI: 0.815-0.916). Exosomal mascRNA expression was higher in patients with MACEs, and patients with high mascRNA exhibited low incidence of MACE-free survival. Cox regression analysis suggested that exosomal mascRNA was independently associated with the risk of MACEs (HR: 3.710, 95% CI: 2.158-6.376, P < 0.001).
Conclusion: Plasma exosomal mascRNA has the potential to function as a diagnostic biomarker for ACS and as a predictor for the incidence of 1-year MACEs.

Keywords:  ACS; acute coronary syndrome; biomarker; exosome; mascRNA

DOI:  https://doi.org/10.2147/IJGM.S538127