Development of a Highly Sensitive Device for Counting the Number of Disease-Specific Exosomes in Human Sera

Kabe, Yoshio; Suematsu, Makoto; Sakamoto, Satoshi; Hirai, Masamichi; Koike, Ikko; Hishiki, Takako; Matsuda, Atsushi; Hasegawa, Yoshinori; Tsujita, Koji; Ono, Masayuki; Minegishi, Naoko; Hozawa, Atsushi; Murakami, Yoshinori; Kubo, Michiaki; Itonaga, Makoto; Handa, Hiroshi

doi:10.1373/clinchem.2018.291963

Cited by 63 publications

(41 citation statements)

References 36 publications

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“…We had developed the exosome-counting system, ExoCounter [ 33 ]. In this system, EVs are captured on antibody-coated optical discs and then labeled with antibody-conjugated magnetic nanobeads (FG beads).…”

Section: Resultsmentioning

confidence: 99%

“…Despite the importance of cancer specific EVs, their accurate quantification in body fluids, such as serum, is difficult due to the small size and containment within lipids or protein aggregates. An exosome counting system, namely ExoCounter (JVC, Yokohama, Japan), that directly detects the absolute number of the disease-specific EVs in serum, has been recently developed [ 33 , 34 ]. Altered glycans associated with several diseases have been reported on the surface of the EVs [ 35 , 36 ].…”

Section: Introductionmentioning

confidence: 99%

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O-Glycan-Altered Extracellular Vesicles: A Specific Serum Marker Elevated in Pancreatic Cancer

Yokose

Kabe

Matsuda

et al. 2020

Cancers

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Pancreatic cancer (PC) is among the most lethal malignancies due to an often delayed and difficult initial diagnosis. Therefore, the development of a novel, early stage, diagnostic PC marker in liquid biopsies is of great significance. In this study, we analyzed the differential glycomic profiling of extracellular vesicles (EVs) derived from serum (two cohorts including 117 PC patients and 98 normal controls) using lectin microarray. The glyco-candidates of PC-specific EVs were quantified using a high-sensitive exosome-counting system, ExoCounter. An absolute quantification system for altered glycan-containing EVs elevated in PC serum was established. EVs recognized by O-glycan-binding lectins ABA or ACA were identified as candidate markers by lectin microarray. Quantitative analyses using ExoCounter revealed that the ABA- or ACA-positive EVs were significantly increased in the culture of PC cell lines or in the serum of PC patients including carbohydrate antigen 19-9 negative patients with high area under curve values. The elevated numbers of EVs in PC serum returned to normal levels after pancreatectomy. Histological examination confirmed that the tumors stained with ABA/ACA. These specific EVs with O-glycans recognized by ABA/ACA are elevated in PC sera and can act as potential biomarkers in a liquid biopsy for PC patients screening.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

O-Glycan-Altered Extracellular Vesicles: A Specific Serum Marker Elevated in Pancreatic Cancer

Yokose

Kabe

Matsuda

et al. 2020

Cancers

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“…Wu et al introduced a method based on the acoustic principle combined with microfluidic technology whereby it would become relatively simple to isolate EVs from whole blood, in a label-free and contact-free manner that would protect the peculiarities, structures and functions of isolated EVs [39]. Another novel technique for EVs purification proposed by Kabe et al [40], consists of a high sensitivity and linearity method from human serum using the properties of magnetic nanobeads and optical disc technology.…”

Section: Evs Isolation and Characterization Methodsmentioning

confidence: 99%

Potential roles of extracellular vesicles in the pathophysiology, diagnosis, and treatment of autoimmune diseases

Tian¹,

Casella²,

Zhang³

et al. 2020

Int. J. Biol. Sci.

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Since extracellular vesicles (EVs) were discovered in 1983 in sheep reticulocytes samples, they have gradually attracted scientific attention and become a topic of great interest in the life sciences field. EVs are small membrane particles, released by virtually every cell that carries a variety of functional molecules. Their main function is to deliver messages to the surrounding area in both physiological and pathological conditions. Initially, they were thought to be either cell debris, signs of cell death, or unspecific structures. However, accumulating evidence support a theory that EVs are a universal mechanism of communication. Thanks to their biological characteristics and functions, EVs are likely to represent a promising strategy for obtaining pathogen information, identifying therapeutic targets and selecting specific biomarkers for a variety of diseases, such as autoimmune diseases. In this review, we provide a brief overview of recent progress in the study of the biology and functions of EVs. We also discuss their roles in diagnosis and therapy, with particular emphasis on autoimmune diseases.

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“…The most widely used NTA determines the number and size of particles by tracking the Brownian motion of single particles in an aqueous solution [66]. Quantification of EVs remains extremely challenging, and new methods, such as nanoflow cytometry, direct stochastic optical reconstruction microscopy, ExoCounter with optical disc technology, and imaging flow cytometry, have been developed to effectively quantify EVs [67][68][69][70]. The purification process can be described as three steps: filtration to remove the cellular debris, concentration of the CM, and exosome isolation from the concentrated CM [71].…”

Section: Quality Control Of Evsmentioning

confidence: 99%

Mesenchymal stem cell-based cell-free strategies: safe and effective treatments for liver injury

Zhao

Zhang

et al. 2020

Stem Cell Res Ther

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Various hepatoxic factors, such as viruses, drugs, lipid deposition, and autoimmune responses, induce acute or chronic liver injury, and 3.5% of all worldwide deaths result from liver cirrhosis, liver failure, or hepatocellular carcinoma. Liver transplantation is currently limited by few liver donors, expensive surgical costs, and severe immune rejection. Cell therapy, including hepatocyte transplantation and stem cell transplantation, has recently become an attractive option to reduce the overall need for liver transplantation and reduce the wait time for patients. Recent studies showed that mesenchymal stem cell (MSC) administration was a promising therapeutic approach for promoting liver regeneration and repairing liver injury by the migration of cells into liver sites, hepatogenic differentiation, immunoregulation, and paracrine mechanisms. MSCs secrete a large number of molecules into the extracellular space, and soluble proteins, free nucleic acids, lipids, and extracellular vesicles (EVs) effectively repair tissue injury in response to fluctuations in physiological states or pathological conditions. Cell-free-based therapies avoid the potential tumorigenicity, rejection of cells, emboli formation, undesired differentiation, and infection transmission of MSC transplantation. In this review, we focus on the potential mechanisms of MSC-based cell-free strategies for attenuating liver injury in various liver diseases. Secretome-mediated paracrine effects participate in the regulation of the hepatic immune microenvironment and promotion of hepatic epithelial repair. We look forward to completely reversing liver injury through an MSC-based cell-free strategy in regenerative medicine in the near future.

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Development of a Highly Sensitive Device for Counting the Number of Disease-Specific Exosomes in Human Sera

Abstract: The ExoCounter system exhibits high performance in the direct detection of exosomes in cell culture and human sera. This method may enable reliable analysis of liquid biopsies.

Cited by 63 publications

References 36 publications

O-Glycan-Altered Extracellular Vesicles: A Specific Serum Marker Elevated in Pancreatic Cancer

O-Glycan-Altered Extracellular Vesicles: A Specific Serum Marker Elevated in Pancreatic Cancer

Potential roles of extracellular vesicles in the pathophysiology, diagnosis, and treatment of autoimmune diseases

Mesenchymal stem cell-based cell-free strategies: safe and effective treatments for liver injury

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