• Title/Summary/Keyword: exosomes

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The potential theragnostic (diagnostic+therapeutic) application of exosomes in diverse biomedical fields

  • Kim, Yong-Seok;Ahn, Jae-Sung;Kim, Semi;Kim, Hyun-Jin;Kim, Shin-Hee;Kang, Ju-Seop
    • The Korean Journal of Physiology and Pharmacology
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    • v.22 no.2
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    • pp.113-125
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    • 2018
  • Exosomes are membranous vesicles of 30-150 nm in diameter that are derived from the exocytosis of the intraluminal vesicles of many cell types including immune cells, stem cells, cardiovascular cells and tumor cells. Exosomes participate in intercellular communication by delivering their contents to recipient cells, with or without direct contact between cells, and thereby influence physiological and pathological processes. They are present in various body fluids and contain proteins, nucleic acids, lipids, and microRNAs that can be transported to surrounding cells. Theragnosis is a concept in next-generation medicine that simultaneously combines accurate diagnostics with therapeutic effects. Molecular components in exosomes have been found to be related to certain diseases and treatment responses, indicating that they may have applications in diagnosis via molecular imaging and biomarker detection. In addition, recent studies have reported that exosomes have immunotherapeutic applications or can act as a drug delivery system for targeted therapies with drugs and biomolecules. In this review, we describe the formation, structure, and physiological roles of exosomes. We also discuss their roles in the pathogenesis and progression of diseases including neurodegenerative diseases, cardiovascular diseases, and cancer. The potential applications of exosomes for theragnostic purposes in various diseases are also discussed. This review summarizes the current knowledge about the physiological and pathological roles of exosomes as well as their diagnostic and therapeutic uses, including emerging exosome-based therapies that could not be applied until now.

Exosomes from Murine-derived GL26 Cells Promote Glioblastoma Tumor Growth by Reducing Number and Function of CD8+T Cells

  • Liu, Zhi-Ming;Wang, Yu-Bin;Yuan, Xian-Hou
    • Asian Pacific Journal of Cancer Prevention
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    • v.14 no.1
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    • pp.309-314
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    • 2013
  • Aim: Brain tumors almost universally have fatal outcomes; new therapeutics are desperately needed and will only come from improved understandins of glioma biology. Methods: Exosomes are endosomally derived 30~100 nm membranous vesicles released from many cell types. Examples from GL26 cells were here purified using density gradient ultracentrifugation and monitored for effects on GL26 tumor growth in C57BL/6j mice (H-2b). Lactate dehydrogenase release assays were used to detect the cytotoxic activity of CD8+T and NK cells. Percentages of immune cells producing intracellular cytokines were analyzed by FACS. Results: In this study, exosomes from murine-derived GL26 cells significantly promoted in vivo tumor growth in GL26-bearing B6 mice. Then we further analyzed the effects of the GL26 cells-derived exosomes on immune cells including CD8+T, CD4+T and NK cells. Inhibition of CD8+T cell cytotoxic activity was demonstrated by CD8+T cell depletion assays in vivo and LDH release assays in vitro. The treatment of mice with exosomes also led to a reduction in the percentages of CD8+T cells in splenocytes as determined by FACS analysis. Key features of CD8+T cell activity were inhibited, including release of IFN-gamma and granzyme B. There were no effects of exosomes on CD4+T cells and NK cells. Conclusion: Based on our data, for the first time we demonstrated that exosomes from murine derived GL26 cells promote the tumor growth by inhibition of CD8+T cells in vivo and thus may be a potential therapeutic target.

Emerging roles of exosomes in cancer invasion and metastasis

  • Soung, Young Hwa;Nguyen, Thalia;Cao, Hans;Lee, Janet;Chung, Jun
    • BMB Reports
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    • v.49 no.1
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    • pp.18-25
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    • 2016
  • Recent evidence has indicated that nano-sized vesicles called "exosomes" mediate the interaction between cancer cells and their microenvironment and play a critical role in the development of cancers. Exosomes contain cargo consisting of proteins, lipids, mRNAs, and microRNAs that can be delivered to different types of cells in nascent as well as distant locations. Cancer cell-derived exosomes (CCEs) have been identified in body fluids such as urine, plasma, and saliva from patients with cancer. Although their content depends on tumor type and stage, CCEs merit consideration as prognostic and diagnostic markers, as vehicles for drug delivery, and as potential therapeutic targets because they could transport various oncogenic elements. In this review, we summarize recent advances regarding the role of CCEs in cancer invasion and metastasis, as well as its potential clinical applications. [BMB Reports 2016; 49(1): 18-25]

Functional Roles of Exosomes in Allergic Contact Dermatitis

  • Bocui Song;Qian Chen;Yuqi Li;Shuang Zhan;Rui Zhao;Xue Shen;Min Liu;Chunyu Tong
    • Journal of Microbiology and Biotechnology
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    • v.32 no.12
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    • pp.1506-1514
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    • 2022
  • Allergic contact dermatitis (ACD) is an allergen-specific T-cell-mediated inflammatory response, albeit with unclear pathogenesis. Exosomes are nanoscale extracellular vesicles secreted by several cell types and widely distributed in various biological fluids. Exosomes affect the occurrence and development of ACD through immunoregulation among other ways. Nevertheless, the role of exosomes in ACD warrants further clarification. This review examines the progress of research into exosomes and their involvement in the pathogenesis, diagnosis, and treatment of ACD and provides ideas for exploring new diagnostic and treatment methods for this disease.

Application of Exosome for Diagnosis and Treatment of Diseases in the Central Nervous System (중추신경계 질환의 진단과 치료를 위한 엑소좀의 활용)

  • Jia Bak;Yun-Sik Choi
    • Journal of Life Science
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    • v.33 no.9
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    • pp.754-765
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    • 2023
  • Exosomes are a type of extracellular vesicle containing proteins and messenger and microRNAs; they are secreted by all cell types. Once released, exosomes are selectively taken up by other cells adjacent or at a distance, releasing their contents and reprogramming the target cells. Since exosomes are natural vesicles produced by cells as small sizes, it is generally accepted that exosomes have a non-toxic nature and non-immunogenic behaviors. Recently, exosomes have elicited scientific attention as drug delivery vehicles to the central nervous system. The central nervous system has a blood-brain barrier that makes it difficult for drugs to penetrate. Thus, the blood-brain barrier has been a major obstacle to the development of drugs for treating neurodegenerative diseases. However, accumulating evidence suggests that exosomes can cross the blood-brain barrier primarily through transcytosis. Consequently, exosomes are expected to become a new delivery vehicle that can cross the blood-brain barrier and deliver drugs into the brain parenchyma. In addition, since different types of exosomes are secreted depending on the cell type and disease state, exosomes can also be utilized as biomarkers for the diagnosis of diseases in the central nervous system. In this review, we summarized recent research trends on exosomes, including clinical trials as biomarkers and treatment options for diseases in the central nervous system.

Immunoaffinity Characteristics of Exosomes from Breast Cancer Cells Using Surface Plasmon Resonance Spectroscopy

  • Sohn, Young-Soo;Na, Wonhwi;Jang, Dae-Ho
    • Journal of Sensor Science and Technology
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    • v.28 no.6
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    • pp.355-359
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    • 2019
  • Exosomes, known as nanoscale extracellular vesicles in the range of 30-150 nm, are known to contain clinically significant information. However, there is still insufficient information on exosomal membrane proteins for cancer diagnosis. In this work, we investigated the characteristics of the membrane proteins of exosomes shed by cultured breast cancer cell lines using a surface plasmon resonance (SPR) spectroscopy and pre-activated alkanethiols modified sensor chips. The antibodies of breast cancer biomarkers such as MCU-16, EpCAM, CD24, ErbB2, and CA19-9 were immobilized on the pre-activated alkanethiols surfaces without any activation steps. The purified exosomes were loaded onto each antibody surface. The affinity rank of the antibody surfaces was decided by the relative capture efficiency factors for the exosomes. In addition, an antibody with a relative capture efficiency close to 100% was tested with exosome concentration levels of 104/µl, 105/µl, and 106/µl for quantitative analysis.

Proteomic Analysis on Exosomes Derived from Patients, Sera Infected with Echinococcus granulosus

  • Wang, Wen;Zhou, Xiaojing;Cui, Fang;Shi, Chunli;Wang, Yulan;Men, Yanfei;Zhao, Wei;Zhao, Jiaqing
    • Parasites, Hosts and Diseases
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    • v.57 no.5
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    • pp.489-497
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    • 2019
  • Cystic echinococcosis (CE), a zoonotic disease caused by Echinococcus granulosus at the larval stage, predominantly develops in the liver and lungs of intermediate hosts and eventually results in organ malfunction or even death. The interaction between E. granulosus and human body is incompletely understood. Exosomes are nanosized particles ubiquitously present in human body fluids. Exosomes carry biomolecules that facilitate communication between cells. To the best of our knowledge, the role of exosomes in patients with CE is not reported. Here, we isolated exosomes from the sera of patients with CE (CE-exo) and healthy donors and subjected them to liquid chromatography-tandem mass spectrometry analysis. Proteomic analysis identified 49 proteins specifically expressed in CE-exo, including 4 proteins of parasitic origin. The most valuable parasitic proteins included tubulin alpha-1C chain and histone H4. And 8 proteins were differentially regulated in CE-exo (fold change>1.5), as analyzed with bioinformatic methods such as annotation and functional enrichment analyses. These findings may improve our understanding about the interaction between E. granulosus and human body, and may contribute to the diagnosis and prevention of CE.

Structural Analysis of Exosomes Using Different Types of Electron Microscopy

  • Choi, Hyosun;Mun, Ji Young
    • Applied Microscopy
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    • v.47 no.3
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    • pp.171-175
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    • 2017
  • Negative staining has been traditionally used for exosome imaging; however, the technique is limited to surface topology only and can cause staining artifacts. Therefore, to analyze the internal structure of exosomes, we employed a method of block preparation, thin sectioning, and electron tomography. In addition, an automatic serial sectioning technique with 15-nm thickness through focused ion beam was employed to observe the three-dimensional structure of exosomes of various sizes. Cryo-transmission electron microscopy revealed the near-to-native structure of exosomes.

Exosomes derived from microRNA-584 transfected mesenchymal stem cells: novel alternative therapeutic vehicles for cancer therapy

  • Kim, Ran;Lee, Seokyeon;Lee, Jihyun;Kim, Minji;Kim, Won Jung;Lee, Hee Won;Lee, Min Young;Kim, Jongmin;Chang, Woochul
    • BMB Reports
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    • v.51 no.8
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    • pp.406-411
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    • 2018
  • Exosomes are small membranous vesicles which contain abundant RNA molecules, and are transferred from releasing cells to uptaking cells. MicroRNA (miRNA) is one of the transferred molecules affecting the adopted cells, including glioma cells. We hypothesized that mesenchymal stem cells (MSCs) can secrete exosomes loading miRNA and have important effects on the progress of gliomas. To determine these effects by treating exosomal miRNA in culture media of miRNA mimic transfected MSCs, we assessed the in vitro cell proliferation and invasion capabilities, and the expression level of relative proteins associated with cell apoptosis, growth and migration. For animal studies, the mice injected with U87 cells were exposed to exosomes derived from miRNA-584-5p transfected MSCs, to confirm the influence of exosomal miRNA on the progress of glioma. Based on our results, we propose a new targeted cancer therapy wherein exosomes derived from miRNA transfected MSCs could be used to modulate tumor progress as the anticancer vehicles.

Rectal cancer-derived exosomes activate the nuclear factor kappa B pathway and lung fibroblasts by delivering integrin beta-1

  • Qingkun Gao;Ke An;Zhaoya Gao;Yanzhao Wang;Changmin Ding;Pengfei Niu;Fuming Lei
    • The Korean Journal of Physiology and Pharmacology
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    • v.27 no.4
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    • pp.375-381
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    • 2023
  • Numerous studies have revealed the importance of tumor-derived exosomes in rectal cancer (RC). This study aims to explore the influence of tumor-derived exosomal integrin beta-1 (ITGB1) on lung fibroblasts in RC along with underlying mechanisms. Exosome morphology was observed using a transmission electron microscope. Protein levels of CD63, CD9, ITGB1, p-p65 and p65 were detected using Western blot. To determine ITGB1's mRNA expression, quantitative real-time polymerase chain reaction was used. Moreover, levels of interleukin (IL)-8, IL-1β, and IL-6 in cell culture supernatant were measured via commercial ELISA kits. ITGB1 expression was increased in exosomes from RC cells. The ratio of p-p65/p65 as well as levels of interleukins in lung fibroblasts was raised by exosomes derived from RC cells, while was reduced after down-regulation of exosomal ITGB1. The increased ratio of p-p65/p65 as well as levels of pro-inflammatory cytokines caused by exosomes from RC cells was reversed by the addition of nuclear factor kappa B (NF-κB) inhibitor. We concluded that the knockdown of RC cells-derived exosomal ITGB1 repressed activation of lung fibroblasts and the NF-κB pathway in vitro.