bims-engexo Biomed News
on Engineered exosomes
Issue of 2024–10–20
ten papers selected by
Ravindran Jaganathan, Universiti Kuala Lumpur
  1. Human mesenchymal stroma/stem-like cell-derived taxol-loaded EVs/exosomes transfer anti-tumor microRNA signatures and express enhanced SDF-1-mediated tumor tropism.
  2. Exosomes from hypoxic urine-derived stem cells facilitate healing of diabetic wound by targeting SERPINE1 through miR-486-5p.
  3. Black-Phosphorus-Reinforced Injectable Conductive Biodegradable Hydrogel for the Delivery of ADSC-Derived Exosomes to Repair Myocardial Infarction.
  4. GPX5-Enriched Exosomes Improve Sperm Quality and Fertilization Ability.
  5. Potential cardiac-derived exosomal miRNAs involved in cardiac healing and remodeling after myocardial ischemia-reperfusion injury.
  6. Role of Exosomes in Salivary Gland Tumors and Technological Advances in Their Assessment.
  7. The integration platform for exosome capture and colorimetric detection: Site occupying effect-modulated MOF-aptamer interaction and aptamer-Au NPs-dopamine interaction.
  8. Macrophages and the Extracellular Matrix.
  9. Exosomes Derived from Bone Marrow Dendritic Cells Exhibit Protective and Therapeutic Potential Against Chemically Induced Chronic Pancreatitis in Rats.
  10. Stem Cell Interventions in Neurology: From Bench to Bedside.
  1. Cell Commun Signal. 2024 Oct 17. 22(1): 506
    Human mesenchymal stroma/stem-like cell-derived taxol-loaded EVs/exosomes transfer anti-tumor microRNA signatures and express enhanced SDF-1-mediated tumor tropism.
    Ralf Hass, Juliane von der Ohe, Tianjiao Luo.
       BACKGROUND: The release of extracellular vesicles (EVs) including exosomes from human mesenchymal stroma/stem-like cells (MSC) represents valuable cell-free carriers for the delivery of regenerative and medicinal compounds.
    METHODS: EVs/exosomes were isolated by differential centrifugation from four individual MSC as controls and after treatment with a sub-lethal concentration of 10 mM taxol for 24 h, respectively. The isolated EVs/exosomes were characterized and quantified by nano-tracking-analysis and by Western blots. MicroRNAs (miRs) were isolated from the different EVs/exosome populations and expression levels were quantified by qPCR using 1246 miR templates. Cytotoxic effects of the different MSC-derived taxol-loaded EVs/exosomes were determined in five different GFP-transduced cancer cell lines and quantified by a fluoroscan assay with a GFP-detecting fluorimeter. The presence of stroma cell-derived factor 1 (SDF-1) in MSC-derived EVs/exosomes and its enhanced expression in the vesicles after taxol treatment of MSC was quantified by a specific ELISA.
    RESULTS: EVs/exosomes isolated from four individual taxol-treated MSC displayed a larger size and higher yields as the control EVs/exosomes and were used as anti-tumor therapeutic vehicles. Application of each of the four MSC-derived taxol-loaded EVs/exosome populations revealed significant cytotoxic effects in cell lines of five different tumor entities (carcinomas of lung, breast, ovar, colon, astrocytoma) in a concentration-dependent manner. Expression analysis of 1246 miRs in these taxol-loaded EVs/exosomes as compared to the corresponding MSC-derived control EVs/exosomes unraveled a taxol-mediated up-regulation of 11 miRs with predominantly anti-tumorigenic properties. Moreover, various constitutively expressed protein levels were unanimously altered in the MSC cultures. Taxol treatment of the different MSC revealed an up-regulation of tetraspanins and a 2.2-fold to 5.4-fold increased expression of SDF-1 among others. Treatment of cancer cells with MSC-derived taxol-loaded EVs/exosomes in the presence of a neutralizing SDF-1 antibody significantly abolished the cytotoxic effects between 20.3% and 27%.
    CONCLUSIONS: These findings suggested a taxol-mediated increase of anti-cancer properties in MSC that enhance the tropism of derived EVs/exosomes to tumors, thereby specifically focusing the therapeutic effects of the delivered products.
    Keywords:  Chemotherapeutics; Exosomes; Extracellular vesicles; Mesenchymal stroma cells; Stroma cell-derived factor; Tumor plasticity; Tumor tropism; microRNAs
    DOI:  https://doi.org/10.1186/s12964-024-01886-2
  2. Biomaterials. 2024 Oct 15. pii: S0142-9612(24)00427-7. [Epub ahead of print]314 122893
    Exosomes from hypoxic urine-derived stem cells facilitate healing of diabetic wound by targeting SERPINE1 through miR-486-5p.
    Ming-Hui Fan, Xiu-Zhen Zhang, Yan-Lin Jiang, Jin-Kui Pi, Ji-Ye Zhang, Yue-Qi Zhang, Fei Xing, Hui-Qi Xie.
      Vascular pathologies and injuries are important factors for the delayed wound healing in diabetes. Previous studies have demonstrated that hypoxic environments could induce formation of new blood vessels by regulating intercellular communication and cellular behaviors. In this study, we have enhanced the angiogenic potential of exosomes by subjecting urine-derived stem cells (USCs) to hypoxic preconditioning. To prolong the retention of exosomes at the wound site, we have also engineered a novel dECM hydrogel termed SISMA, which was modified from porcine small intestinal submucosa (SIS). For its rapid and controllable gelation kinetics, excellent biocompatibility, and exosome release capability, the SISMA hydrogel has proven to be a reliable delivery vehicle for exosomes. The hypoxia-induced exosomes-loaded hydrogel has promoted endothelial cell proliferation, migration, and tube formation. More importantly, as evidenced by significant in vivo vascular regeneration in the early stages post-injury, it has facilitated tissue repair. This may because miR-486-5p in H-exo inhibit SERPINE1 activity in endothelial cell. Additionally, miRNA sequencing analysis suggested that the underlying mechanism for enhanced angiogenesis may be associated with the activation of classical HIF-1α signaling pathway. In summary, our study has presented a novel non-invasive, cell-free therapeutic approach for accelerating diabetes wound healing and development of a practical and efficient exosomes delivery platform.
    Keywords:  Angiogenesis; Diabetic wound; Exosome; Hypoxic; SERPINE1; miR-486–5p
    DOI:  https://doi.org/10.1016/j.biomaterials.2024.122893
  3. ACS Appl Mater Interfaces. 2024 Oct 16.
    Black-Phosphorus-Reinforced Injectable Conductive Biodegradable Hydrogel for the Delivery of ADSC-Derived Exosomes to Repair Myocardial Infarction.
    Hao Wang, Bin Gui, Yueying Chen, Fanglu Zhong, Qianhui Liu, Shiman Zhang, Nan Jiang, Weihai Chen, Chao Xu, Hongjun Yang, Qing Zhou, Qing Deng.
      Myocardial infarction (MI) remains one of the leading causes of death globally, necessitating innovative therapeutic strategies for effective repair. Conventional treatment methods such as pharmacotherapy, interventional surgery, and cardiac transplantation, while capable of reducing short-term mortality rates, still face significant challenges in post-MI repair including the restoration of intercellular biological and electrical signaling. This study presents a novel exosome-loaded conductive hydrogel designed to enhance myocardial repair by concurrently improving biological and electrical signals. Adipose-derived stem cell (ADSC) exosomes, encapsulated within a hyaluronic acid-dopamine (HA-DA) hydrogel, were employed to promote angiogenesis and inhibit inflammation. Incorporating black phosphorus (BP) into the hydrogel improved its electrical conductivity, thereby restoring electrical signal transmission in the infarcted myocardium and preventing arrhythmias. In vitro and in vivo experiments demonstrated that the exosome-loaded conductive hydrogel significantly enhanced cardiac function recovery by accelerating angiogenesis, reducing inflammation, and increasing electrical activity between myocardial cells. The hydrogel exhibited excellent biocompatibility, biodegradability, and sustained release of exosomes, ensuring prolonged therapeutic effects. This integrated approach resulted in notable improvements in the left ventricular ejection fraction, reduced fibrosis, and increased neovascularization. The combination of bioactive exosomes and a conductive hydrogel presents a promising therapeutic strategy for myocardial infarction repair.
    Keywords:  ADSC-derived exosomes; Black phosphorus; Conductive hydrogel; Myocardial infarction repair; Tissue engineering
    DOI:  https://doi.org/10.1021/acsami.4c12285
  4. Int J Mol Sci. 2024 Sep 30. pii: 10569. [Epub ahead of print]25(19):
    GPX5-Enriched Exosomes Improve Sperm Quality and Fertilization Ability.
    Jian Huang, Shuangshuang Li, Yuxuan Yang, Chen Li, Zixi Zuo, Rong Zheng, Jin Chai, Siwen Jiang.
      Semen preservation quality affects the artificial insemination success rate, and seminal exosomes are rich in various proteins that are transferable to sperm and conducive to sperm-function preservation during storage. However, the specific effects of these proteins remain unclear. In this study, the specific effects of these proteins on semen preservation quality and fertilization capacity were investigated through a proteomic analysis of seminal exosomes from boars with high conception rates (HCRs) and low conception rates (LCRs). The results revealed significant differences in the expression of 161 proteins between the two groups, with the GPX5 level being significantly higher in the HCR group (p < 0.05). The role of GPX5 was further investigated by constructing engineered exosomes enriched with GPX5 (Exo-GPX5), which could successfully transfer GPX5 to sperm. Compared to the control group, Exo-GPX5 could significantly improve sperm motility on storage days 4 and 5 and enhance the acrosome integrity on day 5 (p < 0.05). Additionally, Exo-GPX5 increased the total antioxidant capacity (T-AOC) of sperm, reduced the malondialdehyde (MDA) level, and decreased the expression of antioxidant proteins SOD1 and CAT (p < 0.05). In simulated fertilization experiments, Exo-GPX5-treated sperm exhibited higher capacitation ability and a significant increase in the acrosome reaction rate (p < 0.05). Overall, Exo-GPX5 can improve boar semen quality under 17 °C storage conditions and enhance sperm fertilization capacity.
    Keywords:  GPX5; exosomes; liquid storage; semen
    DOI:  https://doi.org/10.3390/ijms251910569
  5. Sci Rep. 2024 10 16. 14(1): 24275
    Potential cardiac-derived exosomal miRNAs involved in cardiac healing and remodeling after myocardial ischemia-reperfusion injury.
    Yu Liu, Jiao Chen, Jian Xiong, Jin-Qun Hu, Li-Yuan Yang, Yu-Xin Sun, Ying Wei, Yi Zhao, Xiao Li, Qian-Hua Zheng, Wen-Chuan Qi, Fan-Rong Liang.
      Migratory cells exist in the heart, such as immune cells, fibroblasts, endothelial cells, etc. During myocardium injury, such as ischemia-reperfusion (MIRI), cells migrate to the site of injury to perform repair functions. However, excessive aggregation of these cells may exacerbate damage to the structure and function of the heart, such as acute myocarditis and myocardial fibrosis. Myocardial injury releases exosomes, which are a type of vesicle with signal transduction function and the miRNA carried by exosomes can control cell migration function. Therefore, regulating this migratory cell population through cardiac-derived exosomal miRNA is crucial for protecting and maintaining cardiac function. Through whole transcriptome RNA sequencing, exosomal miRNA sequencing and single-cell dataset analysis, we (1) determined the potential molecular regulatory role of the lncRNA‒miRNA‒mRNA axis in MIRI, (2) screened four important exosomal miRNAs that could be released by cardiac tissue, and (3) screened seven genes related to cell locomotion that are regulated by four miRNAs, among which Tradd and Ephb6 may be specific for promoting migration of different cells of myocardial tissue in myocardial infarct. We generated a core miRNA‒mRNA network based on the functions of the target genes, which may be not only a target for cardiac repair but also a potential diagnostic marker for interactions between the heart and other tissues or organs. In conclusion, we elucidated the potential mechanism of MIRI in cardiac remodeling from the perspective of cell migration, and inhibition of cellular overmigration based on this network may provide new therapeutic targets for MIRI and to prevent MIRI from developing into other diseases.
    Keywords:  Cell migration; Exosomal miRNA; Locomotion; Myocardial ischemia‒reperfusion injury
    DOI:  https://doi.org/10.1038/s41598-024-75517-8
  6. Cancers (Basel). 2024 Sep 27. pii: 3298. [Epub ahead of print]16(19):
    Role of Exosomes in Salivary Gland Tumors and Technological Advances in Their Assessment.
    Artur Nieszporek, Małgorzata Wierzbicka, Natalia Labedz, Weronika Zajac, Joanna Cybinska, Patrycja Gazinska.
      Backgroud: Salivary gland tumors (SGTs) are rare and diverse neoplasms, presenting significant challenges in diagnosis and management due to their rarity and complexity. Exosomes, lipid bilayer vesicles secreted by almost all cell types and present in all body fluids, have emerged as crucial intercellular communication agents. They play multifaceted roles in tumor biology, including modulating the tumor microenvironment, promoting metastasis, and influencing immune responses. Results: This review focuses on the role of exosomes in SGT, hypothesizing that novel diagnostic and therapeutic approaches can be developed by exploring the mechanisms through which exosomes influence tumor occurrence and progression. By understanding these mechanisms, we can leverage exosomes as diagnostic and prognostic biomarkers, and target them for therapeutic interventions. The exploration of exosome-mediated pathways contributing to tumor progression and metastasis could lead to more effective treatments, transforming the management of SGT and improving patient outcomes. Ongoing research aims to elucidate the specific cargo and signaling pathways involved in exosome-mediated tumorigenesis and to develop standardized techniques for exosome-based liquid biopsies in clinical settings. Conclusions: Exosome-based liquid biopsies have shown promise as non-invasive, real-time systemic profiling tools for tumor diagnostics and prognosis, offering significant potential for enhancing patient care through precision and personalized medicine. Methods like fluorescence, electrochemical, colorimetric, and surface plasmon resonance (SPR) biosensors, combined with artificial intelligence, improve exosome analysis, providing rapid, precise, and clinically valid cancer diagnostics for difficult-to-diagnose cancers.
    Keywords:  biosensor; exosomes; liquid biopsy; saliva; saliva-derived exosomes; salivary gland tumors; tumor microenvironment
    DOI:  https://doi.org/10.3390/cancers16193298
  7. Anal Chim Acta. 2024 Nov 15. pii: S0003-2670(24)01035-3. [Epub ahead of print]1329 343234
    The integration platform for exosome capture and colorimetric detection: Site occupying effect-modulated MOF-aptamer interaction and aptamer-Au NPs-dopamine interaction.
    Jingjing Kuang, Linghao Zhao, Shengli Ruan, Yangkun Sun, Zeyu Wu, Hongyang Zhang, Min Zhang, Ping Hu.
      Exosomes are extracellular vesicles of 30-200 nm in diameter that inherit molecular markers from their parent cells, including proteins, lipids, nucleic acids, and glycoconjugates. The detection and protein profiling of exosome could provide noninvasive access to disease diagnosis and treatment. In recent years, it has been found that Zr-MOFs can capture exosomes by forming Zr-O-P bonds through the phospholipid bilayer of exosomes. In addition, gold nanoparticles with optical response are used for colorimetric biological analysis, such as proteins, peptides, DNA. In this work, we proposed an aptasensor for exosome capture and sensitive colorimetric detection. The Zr-MOF (PCN-224) is innovatively used to capture exosome by Zr-O-P bond, and sodium tripolyphosphate (STPP) is used to block the non-specific adsorption of DNA aptamers on the surface of PCN-224 by site occupying effect. The aptamer binds to exosome immunity, and the remaining aptamer binds to Au NPs, resulting in an increase in steric hindrance and electrostatic repulsion, which makes the dispersion of Au NPs better and avoids the aggregation of Au NPs induced by dopamine (DA). The ratio of absorbance A650/A520 represents the aggregate degree of Au NPs, which correlates with the concentration of exosomes, and achieves sensitive colorimetric detection of exosomes with a linear range of 1.0 × 105-1.0 × 107 particles/mL. Further studies reveal that our work has excellent selectivity and anti-interference, breast cancer patients and healthy individuals can be distinguished by analyzing the differences in the expression of CD63 protein on exosome. The proposed biosensor integrates the capture and detection of exosomes, the multiple colors of Au NPs changed significantly from red to gray, which was conducive to the naked-eye identification of exosome detection.
    Keywords:  Aptamer; AuNPs; Colorimetric; Exosome; Zr-MOF
    DOI:  https://doi.org/10.1016/j.aca.2024.343234
  8. Results Probl Cell Differ. 2024 ;74 55-87
    Macrophages and the Extracellular Matrix.
    William Meza-Morales, Maria Jimenez-Socha, Donald O Freytes, Camilo Mora.
      Macrophages are critical to the immune response, serving multiple essential roles in maintaining tissue homeostasis and providing immune protection. These cells also interact with and influence the extracellular matrix (ECM) by sensing and responding to its components. Such interactions between macrophages and the ECM are mediated through the secretion and uptake of various biomacromolecules, such as cytokines and the extracellular vesicles, including exosomes and microvesicles. These vesicles are pivotal in regulating cellular behaviors that affect the organism's overall function. Moreover, macrophages are integral to the repair mechanisms that alter tissue structure and functionality during tissue remodeling. This chapter will delineate how macrophages interact with the ECM and discuss potential therapeutic strategies leveraging these interactions. It will conclude with a discussion of the challenges ahead, highlighting the importance of understanding macrophage-ECM dynamics for advancing basic biology and clinical applications.
    Keywords:  Extracellular matrix; Extracellular vesicles; Macrophages; Tissue regeneration
    DOI:  https://doi.org/10.1007/978-3-031-65944-7_2
  9. Inflammation. 2024 Oct 19.
    Exosomes Derived from Bone Marrow Dendritic Cells Exhibit Protective and Therapeutic Potential Against Chemically Induced Chronic Pancreatitis in Rats.
    Shaimaa M Bashir, Sherine M Rizk, Mohammed M Nooh, Hebatullah S Helmy.
       BACKGROUND: Chronic pancreatitis (CP) is a specific clinical disorder that develops from pancreatic fibrosis and immune cell dysregulation. It has been proposed that bone marrow dendritic cells (BMDCs) exosomes have significant effects on immune regulation. Thus, the current study acquainted the prophylactic and therapeutic effects of exosomes derived from BMDCs on a rat model of CP.
    MATERIALS AND METHODS: BMDCs were prepared and identified, and then the exosomes were isolated by differential ultracentrifugation. Prophylactic and therapeutic effects of exosomes were investigated on L-arginine induced CP model.
    RESULTS: Administration of two tail vein injections of exosomes (200 μg/kg/dose suspended in 0.2 ml PBS) markedly improved the pancreatic function and histology compared to CP group. Moreover, exosomes prominently mitigated the increase in amylase, lipase, tumor necrosis factor-α (TNF-α), transforming growth factor-β (TGF-β) and elevated antioxidant enzymes; catalase, superoxide dismutase (SOD) and glutathione peroxidase (GPx).
    CONCLUSION: BMDCs exosomes can be considered as a promising candidate, with a high efficacy and stability compared with its parent cell, for management of CP and similar inflammatory diseases.
    Keywords:  Chronic pancreatitis; Dendritic cells; Exosomes
    DOI:  https://doi.org/10.1007/s10753-024-02150-y
  10. J Alzheimers Dis. 2024 ;101(s1): S395-S416
    Stem Cell Interventions in Neurology: From Bench to Bedside.
    Miguel A Pappolla, Ping Wu, Xiang Fang, Burkhard Poeggeler, Kumar Sambamurti, Thomas Wisniewski, George Perry.
      Stem cell therapies are progressively redefining the treatment landscape for a spectrum of neurological and age-related disorders. This review discusses the molecular and functional attributes of stem cells, emphasizing the roles of neural stem cells and mesenchymal stem cells in the context of neurological diseases such as stroke, multiple sclerosis, amyotrophic lateral sclerosis, traumatic brain injury, Parkinson's disease, and Alzheimer's disease. The review also explores the potential of stem cells in addressing the aging process. The paper analyzes stem cells' intrinsic properties of self-renewal, differentiation, and paracrine effects, alongside the importance of laboratory-modified stem cells like induced pluripotent stem cells and transgenic stem cells. Insights into disease-specific stem cell treatments are offered, reviewing both successes and challenges in the field. This includes the translational difficulties from rodent studies to human trials. The review concludes by acknowledging the uncharted territories that warrant further investigation, emphasizing the potential roles of stem cell-derived exosomes and indole-related molecules, and aiming at providing a basic understanding of stem cell therapies.
    Keywords:  Alzheimer’s disease; Parkinson’s disease; amyotrophic lateral sclerosis; multiple sclerosis; regenerative medicine; stem cells; stroke; traumatic brain injury
    DOI:  https://doi.org/10.3233/JAD-230897
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