A5067846549- 3D Printing in Biomedical Research
- Pluripotent Stem Cells Research
- Cancer Cells and Metastasis
- Barrier Structure and Function Studies
- Digestive system and related health
- Tissue Engineering and Regenerative Medicine
- Liver physiology and pathology
- Pancreatic function and diabetes
- Kidney Stones and Urolithiasis Treatments
- Angiogenesis and VEGF in Cancer
- Colorectal Cancer Treatments and Studies
- Pharmacogenetics and Drug Metabolism
- Cancer Treatment and Pharmacology
- Receptor Mechanisms and Signaling
- Neurological Disease Mechanisms and Treatments
- Pancreatitis Pathology and Treatment
- Liver Disease Diagnosis and Treatment
- Hormonal Regulation and Hypertension
- Growth Hormone and Insulin-like Growth Factors
- Cerebrospinal fluid and hydrocephalus
- Estrogen and related hormone effects
- Chronic Kidney Disease and Diabetes
- Chemotherapy-induced cardiotoxicity and mitigation
- Biomedical Ethics and Regulation
- Hepatitis B Virus Studies
Nagoya City University
2018-2024
Gunma University Hospital
2012-2017
Gunma University
2013-2014
Shinshu University
2012
University of Toyama
2008
Tohoku Medical and Pharmaceutical University
2004
Intestinal organoids morphologically resemble intestinal tissues and are expected to be used in both regenerative medicine drug development studies, including pharmacokinetic studies. However, the properties of these remain poorly characterized. In this study, we aimed generate pharmacokinetically functional from human induced pluripotent stem (iPS) cells. Human iPS cells were differentiate into midgut then seeded on EZSPHERE plates (AGC Techno Glass Inc., Shizuoka, Japan) uniform spheroids,...
Abstract Background Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes disease 2019 (COVID-19), which is associated with various neurological symptoms, including nausea, dizziness, headache, encephalitis, and epileptic seizures. SARS-CoV-2 considered to affect the central nervous system (CNS) by interacting blood–brain barrier (BBB), defined tight junctions that seal paracellular gaps between brain microvascular endothelial cells (BMECs). Although infection of BMECs has been...
In the past decade, molecular-targeted drugs have been focused upon for treatment of cancer. 2002, gefitinib, an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor became available in Japan non-small cell lung cancer (NSCLC). Over 80% selected patients, such as EGFR mutation-positive respond to gefitinib treatment; however, most patients develop acquired resistance within a few years. Recently, many studies performed determine precisely how select who will best timing its...
Inflammatory bowel disease, which typically manifests as Crohn’s disease and ulcerative colitis, is caused by the abnormal production of cytokines such tumor necrosis factor (TNF)-α transforming growth (TGF)-β. These damage intestinal epithelial cells trigger fibrosis, respectively, for current in vitro models have many limitations. Therefore, we tested whether human induced pluripotent stem cell-derived organoids (HiOs) can mimic inflammatory (IBD), a model suitable drug screening. HiOs...
Abstract Background The blood–brain barrier (BBB) plays an important role as a biological by regulating molecular transport between circulating blood and the brain parenchyma. In drug development, accurate evaluation of BBB permeability is essential to predict not only efficacy but also safety drugs. Recently, microvascular endothelial-like cells derived from human induced pluripotent stem (iPSCs) have attracted much attention. However, differentiation protocol has been optimized,...
Abstract Background In vitro blood–brain barrier (BBB) models using human induced pluripotent stem (iPS) cell-derived brain microvascular endothelial-like cells (iBMELCs) have been developed to predict the BBB permeability of drug candidates. For differentiation iBMELCs, Matrigel, which is a gelatinous protein mixture, often used as coating substrate. However, components Matrigel can vary among lots, it obtained from mouse sarcoma with use special technics and also contains various basement...
The purpose of this study was to describe the impact sex and cytochrome P450 3A5 (CYP3A5) variant on blood concentration tacrolimus in patients with systemic lupus erythematosus or rheumatoid arthritis. (ng/mL) divided by daily dose (mg/day) patient's weight (kg) (C/D) obtained from 55 patients. C/D value analysed according genetic variation CYP3A5 ATP binding cassette subfamily B member 1 (ABCB1), sex, age. CYP3A5*3/*3 group significantly higher than CYP3A5*1/*1 *1/*3 groups (p < 0.05,...
The endoderm, differentiated from human induced pluripotent stem cells (iPSCs), can differentiate into the small intestine and liver, which are vital for drug absorption metabolism. development of iPSC-derived enterocytes (HiEnts) hepatocytes (HiHeps) has been reported. However, pharmacokinetic function-deficiency these remains to be elucidated. Here, we aimed develop an efficient differentiation method induce endoderm formation iPSCs. Cells treated with activin A 168 h expressed higher...
Ulcerative colitis (UC) is an inflammatory bowel disease characterized by repeated remissions and relapses. Immunosuppressive drugs have facilitated the induction maintenance of remission in many patients with UC. However, immunosuppressive cannot directly repair impaired intestinal mucosa are insufficient for preventing relapse. Therefore, new treatment approaches to damaged epithelium UC been attempted through transplantation organoids, which can be differentiated into embedding Matrigel,...
Hepatitis B virus (HBV) specifically infects human hepatocytes and increases the risks of cirrhosis liver cancer. Currently, nucleic acid analogs are main therapeutics for chronic hepatitis caused by HBV infection. Although can eliminate DNA inhibiting reverse transcriptase, they cannot lead to negative conversion covalently closed circular (cccDNA) surface antigen (HBsAg). In this study, we revealed that antifilarial drug ivermectin suppresses production a different mechanism from analog...
The regulation mechanism of female-predominant expression the mouse <i>Cyp2b9</i> gene was investigated in vivo and vitro. Luciferase reporter assay revealed that –234/–194 region may be responsible for sexually dimorphic expression. There is a predicted forkhead box A2 (FoxA2) (hepatic nuclear factor 3β)-binding site this region. Chromatin immunoprecipitation indicated binding protein to FoxA2 5-week-old female mice, whereas found both sexes at age 3 weeks, accordance with our previous...
Endothelial cells (ECs) and endothelial progenitor (EPCs) play crucial roles in maintaining vascular health homeostasis. Both cell types have been used regenerative therapy as well various vitro models; however, the properties of primary human ECs EPCs are dissimilar owing to differences genetic backgrounds sampling techniques. Human induced pluripotent stem (hiPSCs) an alternative source EPCs. However, low purity differentiated from hiPSCs, purification via antigen-antibody reaction, which...
Abstract Our previous study showed that the flotillin level is decreased in blood of patients with Alzheimer’s disease (AD) when compared to non-AD and vascular dementia; however, molecular mechanism remains be determined. In this study, elucidate whether Aβ accumulation brain has an effect on level, we used our previously established blood–brain barrier (BBB) culture model using microvascular endothelial cells obtained from human induced pluripotent stem (iBMECs) astrocytes prepared rat...
Abstract The ultimate goal of regenerative medicine is the transplantation a target organ generated by patient's own cells. Recently, method generation using pluripotent stem cells ( PSC s) and blastocyst complementation was reported. This approach based on chimeric animal an early embryo s, contribution s to key method's success. However, rate in organs different methods remains unknown. In this study, we used 8‐cell aggregation, injection, injection generate interspecies mice rat embryonic...
The small intestine plays an important role in the pharmacokinetics of orally administered drugs due to presence drug transporters and drug-metabolizing enzymes. However, few appropriate methods exist investigate intestinal pharmacokinetics. Induced pluripotent stem (iPS) cells can form various types represent a potentially useful tool for discovery. We previously reported that differentiated enterocytes from human iPS are pharmacokinetic studies; however, process is time resource intensive....
Ethanol is included in certain injectable preparations of anticancer drugs to increase their solubility. Since the volume ethanol these approximately half total injection volume, potential inhibitory effects on central nervous system cannot be disregarded, especially considering that patients may drive immediately after administration medication. Therefore, concentration was examined exhaled breath paclitaxel, an medication containing ethanol. The intravenous infusion paclitaxel measured 30...
CYP3A44 and CYP3A41 are female-specific CYP3A in the mouse liver. In primary cultured hepatocytes, dexamethasone concentration-dependently induced mRNA, highest response was seen at 10<sup>-5</sup> M. contrast, mRNA expression lower concentrations (10<sup>-7</sup> or 10<sup>-6</sup> M). At submicromolar concentration M), induction of very slight, but strongly enhanced observed by simultaneous addition growth hormone (GH). Similar enhancement also expression. Continuous exposure to GH, which...
We previously discovered that renal macrophages (Mφs) phagocytose calcium oxalate monohydrate (COM) crystals. This study investigated the processing of engulfed crystals using in vitro models.J774.1 mouse Mφs were exposed to COM and observed for 24 h polarized light microscopy with/without cytochalasin B (CB), an inhibitor phagocytosis, confirm active crystal phagocytosis. LysoTracker immunohistochemical staining transmission electron lysosomal-associated membrane protein 1 used uptake into...
In this study we report the pharmacokinetics and severe adverse effects of sunitinib in a woman with gastrointestinal stromal tumor (GIST). A 60-year-old small intestinal GIST developed thrombocytopenia (1.7×10(4)/μl) following 1 week treatment at 50 mg/day. Although dose was reduced to 25 mg/day, platelet levels remained low. On day 7, trough concentration plus SU12662 46.1 ng/ml area under curve (AUC) 1,393.0 ng·h/l. The again 12.5 However, after resumption treatment, patient symptoms left...
In preclinical studies, the cynomolgus monkey (CM) model is frequently used to predict pharmacokinetics of drugs in human small intestine, because its evolutionary closeness humans. Intestinal organoids that mimic intestinal tissue have attracted attention regenerative medicine and drug development. this study, we generated from CM induced pluripotent stem (CMiPS) cells analyzed their pharmacokinetic functions. CMiPS were into hindgut; then, seeded on microfabricated culture vessel plates...