Publications by authors named "Takahiro Ochiya"

Unlabelled: Adipose-derived stem cells (ASCs) and their small extracellular vesicles (sEVs) hold significant potential for regenerative medicine due to their tissue repair capabilities. The microRNA (miRNA) content in sEVs varies depending on ASC status; however, the effects of aging and cell passage on miRNA profiles remain unclear. In this study, we examined the effects of donor age and cell expansion on ASC characteristics and transcriptome using ASCs obtained from three young and three old donors.

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Article Synopsis
  • The study focused on chemically induced liver progenitors (CLiP) derived from steatotic livers in miniature pigs to assess their potential for future liver disease treatment.
  • CLiP from steatotic livers showed a higher ability to proliferate compared to those from healthy livers, but only the normal group demonstrated mature liver cell functionality after re-differentiation.
  • Despite the lower production of extracellular vesicles (EVs) in the disease group, the overall findings suggest that CLiP from steatotic livers could be a viable option for cell therapy in liver disease patients.
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Background: Platinum chemotherapy is the cornerstone of treatment for high-grade serous ovarian cancer (HGSOC); however, validated biomarkers that can accurately predict platinum response are lacking. Based on their roles in the underlying pathophysiology, circulating microRNAs are potential, noninvasive biomarkers in cancer. In the present study, we aimed to evaluate the circulating miRNA profiles of patients with HGSOC and to assess their potential utility as biomarkers to predict platinum response.

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Medication-related osteonecrosis of the jaw (MRONJ) is an intractable form of osteonecrosis of the jaw that rarely occurs in patients using bone resorption inhibitors such as bisphosphonates (BPs). Then, extracellular vesicles (EVs) carry various signaling molecules, such as mRNAs, microRNAs (miRNAs), and proteins, and have attracted attention as intercellular communication tools. Recently, the role of EVs in communication between osteoclasts and surrounding bone cells has been confirmed.

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Exosomes are small extracellular vesicles (sEVs) secreted via multivesicular bodies (MVBs)/late endosomes and mediators of cell-cell communication. We previously reported a novel post-translational modification by ubiquitin-like 3 (UBL3). UBL3 is localized in MVBs and the plasma membrane and released outside as sEVs, including exosomes.

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Multiple microRNAs encapsulated in extracellular vesicles (EVs) including exosomes, unique subtypes of EVs, differ in healthy and cancer groups of people, and they represent a warning sign for various cancer scenarios. Since all EVs in blood cannot be transferred from donor to recipient cells during a single blood circulation, kidney filtration could pass some untransferred EVs from blood to urine. Previously, we reported on the ability of zinc oxide nanowires to capture EVs based on surface charge and hydrogen bonding; these nanowires extracted massive numbers of microRNAs in urine, seeking cancer-related microRNAs through statistical analysis.

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The lack of circulating biomarkers for tumor monitoring is a major problem in Ewing sarcoma management. The development of methods for accurate tumor monitoring is required, considering the high recurrence rate of drug-resistant Ewing sarcoma. Here, we describe a sensitive analytical technique for tumor monitoring of Ewing sarcoma by detecting circulating extracellular vesicles secreted from Ewing sarcoma cells.

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Risk factors for hepatocarcinogenesis include chronic inflammation due to viral infection, liver fibrosis, and aging. In this study, we separated carcinogenic and non-carcinogenic cases due to hepatitis C virus (HCV) infection, aiming to comprehensively analyze miRNA expression in liver tissues by age, and identify factors that contribute to carcinogenesis. Total RNA was extracted from 360 chronic hepatitis C (CH), 43 HCV infected hepatocellular carcinoma (HCC), and surrounding non-tumor (SNT) tissues.

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Cancer cells secrete extracellular vesicles (EVs) to regulate cells in the tumor microenvironment to benefit their own growth and survive in the patient's body. Although emerging evidence has demonstrated the molecular mechanisms of EV release, regulating cancer-specific EV secretion remains challenging. In this study, we applied a microRNA library to reveal the universal mechanisms of EV secretion from cancer cells.

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Background: Numerous chemical reprogramming techniques have been reported, rendering them applicable to regenerative medicine research. The aim of our study was to evaluate the therapeutic potential of human CLiP derived from clinical specimens transplanted into a nonalcoholic steatohepatitis (NASH) mouse model of liver fibrosis.

Methods: We successfully generated chemically induced liver progenitor (CLiP), which exhibited progenitor-like characteristics, through stimulation with low-molecular-weight compounds.

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Cardiac fibrosis is a common pathological feature of cardiovascular diseases that arises from the hyperactivation of fibroblasts and excessive extracellular matrix (ECM) deposition, leading to impaired cardiac function and potentially heart failure or arrhythmia. Extracellular vesicles (EVs) released by cardiomyocytes (CMs) regulate various physiological functions essential for myocardial homeostasis, which are disrupted in cardiac disease. Therefore, healthy CM-derived EVs represent a promising cell-free therapy for the treatment of cardiac fibrosis.

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Purpose Of Review: We discussed the challenges associated with the clinical application of extracellular vesicles and summarized their potential impact on oncological clinical practice in urology.

Recent Findings: Despite extensive research on extracellular vesicles, their clinical applications remain limited; this is likely to be because of small study cohorts, a lack of large-scale analyses, and the impact of variable extraction and storage methods on analysis outcomes. However, promising results have emerged from clinical trials targeting urinary extracellular vesicles in prostate cancer using ExoDx Prostate Test.

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Acute lung injury (ALI) is characterized by respiratory failure resulting from the disruption of the epithelial and endothelial barriers as well as immune system. In this study, we evaluated the therapeutic potential of airway epithelial cell-derived extracellular vesicles (EVs) in maintaining lung homeostasis. We isolated human bronchial epithelial cell-derived EVs (HBEC-EVs), which endogenously express various immune-related surface markers and investigated their immunomodulatory potential in ALI.

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Article Synopsis
  • * Researchers assessed 108 patients with advanced disease, matching those who underwent surgery or chemotherapy, and identified specific microRNAs that predicted progression-free survival for each treatment option.
  • * Results showed that while some microRNAs correlated with successful surgery outcomes, there was no significant difference in actual versus estimated survival between the two treatments, suggesting that microRNA profiles might assist in patient treatment selection.
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  • - Prostate cancer (PCa) is the second most prevalent cancer among men in the U.S., facing challenges with drug resistance and detection, prompting a focus on extracellular vesicles (EVs) that may play important roles in cancer biology.
  • - EVs contain various biological materials like proteins and RNA that influence tumor behavior, immune responses, and cancer progression, highlighting their potential as stable biomarkers for liquid biopsies in PCa.
  • - The review emphasizes that while current knowledge on EVs in PCa management is limited, ongoing research may lead to innovative therapies and improved outcomes for patients.
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Among the analytes circulating in body fluids, microRNAs, a type of non-coding RNA and known to exist 2655 in primates, have attracted attention as a novel biomarker for cancer screening. MicroRNAs are signaling molecules with important gene expression regulatory functions that can simultaneously control many gene functions and multiple different pathways in living organisms. These microRNAs are transported in extracellular vesicles (EVs), which are lipid bilayers with 50-150 nm in diameter, and are used as communication tools between cells.

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Tumor tissue is densely packed with cancer cells, non-cancerous cells, and ECM, forming functional structures. Cancer cells transfer extracellular vesicles (EVs) to modify surrounding normal cells into cancer-promoting cells, establishing a tumor-favorable environment together with other signaling molecules and structural components. Such tissue environments largely affect cancer cell properties, and so as EV-mediated cellular communications within tumor tissue.

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  • The article discusses the use of liquid biopsy, focusing on non-coding RNAs and extracellular vesicles as non-invasive tools for diagnosing and managing breast cancer.
  • These molecules play crucial roles in early detection, treatment monitoring, and prognosis of the disease.
  • The discussion emphasizes their unique characteristics and potential future contributions to breast cancer diagnostics and therapies.
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There is an unmet need for antifibrotic therapies to prevent the progression of liver cirrhosis. Previously, we conducted an exploratory trial to assess the safety and antifibrotic efficacy of PRI-724, a selective CBP/β-catenin inhibitor, in patients with liver cirrhosis. PRI-724 was well tolerated and exerted a potential antifibrotic effect.

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Article Synopsis
  • * Despite advancements in understanding EV biology and methodology, challenges persist in areas like nomenclature, separation, and characterization, hindering their application in research and clinical settings.
  • * The International Society for Extracellular Vesicles (ISEV) has released the updated 'Minimal Information for Studies of Extracellular Vesicles' (MISEV2023) to guide researchers on best practices for EV research, encompassing the latest techniques and addressing various methods of EV production and study.
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Background And Aim: Circulating micro RNAs (miRNAs) indicate clinical pathologies such as inflammation and carcinogenesis. In this study, we aimed to investigate whether miRNA expression level patterns in could be used to diagnose hepatocellular carcinoma (HCC) and biliary tract cancer (BTC), and the relationship miRNA expression patterns and cancer etiology.

Methods: Patients with HCC and BTC with indications for surgery were selected for the study.

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Article Synopsis
  • Breast cancer has a rising incidence and high mortality rate, primarily due to its tendency to metastasize, especially to the brain, which worsens patient outcomes.
  • Extracellular vesicles (EVs) are small vesicles released by cells that carry important biomolecules, influencing cellular communication and processes.
  • This review explores how EVs contribute to the spread of breast cancer to the brain, while also considering the potential of EVs as targets for therapy and as early markers for diagnosing brain metastasis in breast cancer.
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Purpose: To estimate the roles of extracellular vesicles (EVs) in tears and to determine whether their profiles are associated with the type of ocular disease.

Study Design: Cross-sectional study.

Methods: Tear EVs were extracted from 14 healthy participants and from 21 patients with retinal diseases (age-related macular degeneration [AMD] or diabetic macular edema [DME]).

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Background: The progression of liver fibrosis leads to portal hypertension and liver dysfunction. However, no antifibrotic agents have been approved for cirrhosis to date, making them an unmet medical need. Small extracellular vesicles (sEVs) of mesenchymal stem cells (MSCs) are among these candidate agents.

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