A5005400408- Pluripotent Stem Cells Research
- CRISPR and Genetic Engineering
- Evolutionary Algorithms and Applications
- 3D Printing in Biomedical Research
- Metaheuristic Optimization Algorithms Research
- Fuzzy Logic and Control Systems
- Biomedical Ethics and Regulation
- Virus-based gene therapy research
- Ion Channels and Receptors
- Mitochondrial Function and Pathology
- Renal and related cancers
- Stock Market Forecasting Methods
- Advanced Multi-Objective Optimization Algorithms
- Cardiac electrophysiology and arrhythmias
- Neural Networks and Applications
- Viral Infectious Diseases and Gene Expression in Insects
- Legionella and Acanthamoeba research
- Traffic control and management
- ATP Synthase and ATPases Research
- Cardiac Ischemia and Reperfusion
- Mesenchymal stem cell research
- Vibrio bacteria research studies
- Fungal and yeast genetics research
- Escherichia coli research studies
- Hepatitis B Virus Studies
National Institute of Health Sciences
2015-2024
Omron (Japan)
2018
Foundation for Biomedical Research and Innovation
2012-2015
Osaka University
2006-2015
Kyushu University
2009-2013
Foundation for Biomedical Research
2013
Japan Science and Technology Agency
2011
Nagoya University
1987-2010
Osaka Prefecture University
2003
Human induced pluripotent stem cells (hiPSCs) possess the capabilities of self-renewal and differentiation into multiple cell types, they are free ethical problems associated with human embryonic (hESCs). These characteristics make hiPSCs a promising choice for future regenerative medicine research. There significant obstacles, however, preventing clinical use hiPSCs. One most obvious safety issues is presence residual undifferentiated that have tumorigenic potential. To locate cells, in...
Abstract Reactive oxygen species (ROS) produced by NADPH oxidase 2 (Nox2) function as key mediators of mechanotransduction during both physiological adaptation to mechanical load and maladaptive remodeling the heart. This is despite low levels cardiac Nox2 expression. The mechanism underlying transition from maladaptation remains obscure, however. We demonstrate that transient receptor potential canonical 3 (TRPC3), a Ca 2+ -permeable channel, acts positive regulator ROS (PRROS) in...
Abstract Structural cardiac remodeling, accompanying cytoskeletal reorganization of cells, is a major clinical outcome diastolic heart failure. A highly local Ca 2+ influx across the plasma membrane has been suggested to code signals induce Rho GTPase-mediated fibrosis, but it obscure how specifically decodes as reorganizing signal under conditions rhythmic handling required for pump function. We found that an inhibition transient receptor potential canonical 3 (TRPC3) channel activity...
Human induced pluripotent stem cells (hiPSCs) represent promising raw materials of human cell-based therapeutic products (hCTPs). As undifferentiated hiPSCs exhibit intrinsic tumorigenicity properties that enable them to form teratomas, hCTPs containing residual may cause tumor formation following transplantation. We first established quantitative and sensitive testing dissociated into single using NOD/Shi-scid IL2Rγnull (NOG) mice by inhibiting apoptosis with a Rho kinase inhibitor. To...
Innovative applications of cell therapy products (CTPs) derived from human pluripotent stem cells (hPSCs) in regenerative medicine are currently being developed. The presence residual undifferentiated hPSCs CTPs is a quality concern associated with tumorigencity. However, no simple vitro method for direct detection that contaminate has been Here, we show novel approach and sensitive trace amount induced (hiPSCs) using highly efficient amplification combination laminin-521 Essential 8 medium....
Human pluripotent stem cells (hPSCs), such as human embryonic (hESCs) and induced (hiPSCs), are leading candidate raw materials for cell therapy products, because of their capacity differentiation unlimited self-renewal. hPSC-derived products have already entered the scope clinical application. However, assessment control tumorigenicity remains to be a critical challenge. Sensitive detection cellular impurities is necessary safety quality products. In present study, we established sensitive...
The contamination of human cell-processed therapeutic products (hCTPs) with tumorigenic cells is one the major concerns in manufacturing and quality control hCTPs. However, no quantitative method for detecting cellular impurities currently standardized. NOD/Shi-scid IL2Rγnull (NOG) mice have shown high xeno-engraftment potential compared other well-known immunodeficient strains, e.g. nude mice. Hypothesizing that tumorigenicity test using NOG could be a sensitive to detect small amount...
Abstract The human pathogen Legionella pneumophila delivers a large array of the effector proteins into host cells using Dot/Icm type IVB secretion system. Among composing system, an inner membrane protein DotI is known to be crucial for function but its structure and role in IV had not been elucidated. We report here crystal structures periplasmic domains ortholog conjugation system plasmid R64, TraM. These reveal striking similarity VirB8, component IVA systems, suggesting that DotI/TraM...
Mitochondria of the yeast Saccharomyces cerevisiae contain enzymes Crd1p and Psd1p, which synthesize cardiolipin (CL) phosphatidylethanolamine respectively. A previous study indicated that crd1Δ is synthetically lethal with psd1Δ. In this study, to identify novel genes involved in CL metabolism, we searched for genetically interact found deletion FMP30 encoding a mitochondrial inner membrane protein results synthetic growth defect Although fmp30Δ cells grew normally exhibited slightly...
Abstract Human multipotent mesenchymal stromal/stem cells (MSCs) have been utilized in cell therapy for various diseases and their clinical applications are expected to increase the future. However, variation MSC-based product quality due MSC heterogeneity has resulted significant constraints utility of MSCs. Therefore, we hypothesized that it might be important identify ensure/enrich suitable subpopulations therapies using products. In this study, aimed functional predict efficacy...
Abstract Contamination with tumorigenic cellular impurities is one of the most pressing concerns for human cell-processed therapeutic products (hCTPs). The soft agar colony formation (SACF) assay, which a well-known in vitro assay detection malignant transformed cells, applicable quality assessment hCTPs. Here we established an image-based screening system SACF using high-content cell analyzer termed digital assay. Dual fluorescence staining formed colonies and dissolution led to accurate...
Clinical applications of human induced pluripotent stem cells (hiPSCs) are expected, but hiPSC lines vary in their differentiation propensity. For efficient selection suitable for into desired cell lineages, here we identify SALL3 as a marker to predict expression hiPSCs correlates positively with ectoderm capacity and negatively mesoderm/endoderm capacity. Without affecting self-renewal hiPSCs, knockdown inhibits conversely enhances mesodermal/endodermal differentiation. Similarly, loss-...
Abstract Baroreflex control of cardiac contraction (positive inotropy) through sympathetic nerve activation is important for cardiocirculatory homeostasis. Transient receptor potential canonical subfamily (TRPC) channels are responsible α 1 -adrenoceptor (α AR)-stimulated cation entry and their upregulation associated with pathological remodeling. Whether TRPC participate in physiological pump functions remains unclear. We demonstrate that TRPC6-specific Zn 2+ influx potentiates...
Human pluripotent stem cells (hPSCs) are leading candidate raw materials for cell-based therapeutic products (CTPs). In the development of hPSC-derived CTPs, it is imperative to ensure that they do not form tumors after transplantation safety reasons. Because cellular immortalization a landmark malignant transformation and common feature cancer cells, we aimed develop an in vitro assay detecting immortalized CTPs. We employed retinal pigment epithelial (RPE) as model identified gene encoding...
We propose a hybrid algorithm of fuzzy versions two genetics-based machine learning approaches: Michigan and Pittsburgh approaches. First, we examine the performance each approach by computer simulations on commonly used data sets. Simulation results clearly demonstrate that has its own advantages disadvantages. While high search ability to efficiently find good rules in large spaces for high-dimensional pattern classification problems, it can not directly optimize rule-based systems. On...
The Multisite Evaluation Study on Analytical Methods for Non-Clinical Safety Assessment of Human-Derived Regenerative Medical Products (MEASURE) is a Japanese experimental public-private partnership initiative, which aims to standardize methodology tumorigenicity evaluation human pluripotent stem cell (hPSC)-derived therapy products (CTPs). Undifferentiated hPSCs possess tumorigenic potential, and thus residual undifferentiated are one the major hazards risk tumor formation from hPSC-derived...
Abstract Selection of human induced pluripotent stem cell (hiPSC) lines with high cardiac differentiation potential is important for regenerative therapy and drug screening. We aimed to identify biomarkers predicting hiPSC by comparing the gene expression profiles six undifferentiated different capabilities. used three platforms analysis, namely, cap analysis (CAGE), mRNA array, microRNA array efficiently screen related hiPSCs. Statistical revealed candidate biomarker genes significant...
Despite the development of various in vitro differentiation protocols for efficient derivation specific cell types, human induced pluripotent stem (hiPSC) lines have varing ability to differentiate into lineages. Therefore, surrogate markers accurately predicting propensity hiPSC may facilitate cell-based therapeutic product and manufacture. We attempted identify marker genes that could predict hiPSCs neural stem/progenitor cells (NS/PCs). Using Spearman's rank correlation coefficients, we...
In this paper, we propose a hybrid genetics-based machine learning algorithm for designing linguistic classification system that consists of small number fuzzy if-then rules with clear interpretation. Our task is to generate from numerical data high-dimensional pattern problem. We assume set values given each attribute the problem by human experts. Thus our described as finding combinations values, which used antecedent part rule. While seems be simple at glance, it very difficult especially...
Abstract Cell-processed therapeutic products (CTPs) derived from human pluripotent stem cells (hPSCs) have innovative applications in regenerative medicine. However, undifferentiated hPSCs possess tumorigenic potential; thus, sensitive methods for the detection of residual are essential clinical use hPSC-derived CTPs. The limit currently available is 1/10 5 (0.001%, hPSCs/differentiated cells) or more, which could be insufficient when CTPs contain more than 1 × 10 cells. In this study, we...