A5064502673- Tissue Engineering and Regenerative Medicine
- Pluripotent Stem Cells Research
- 3D Printing in Biomedical Research
- CRISPR and Genetic Engineering
- Cardiomyopathy and Myosin Studies
- Neuroscience and Neural Engineering
- Cardiac Structural Anomalies and Repair
- Electrospun Nanofibers in Biomedical Applications
- Connexins and lens biology
- Cardiac Fibrosis and Remodeling
- Congenital heart defects research
- Mechanical Circulatory Support Devices
- Extracellular vesicles in disease
- Cardiac electrophysiology and arrhythmias
- Cardiovascular Effects of Exercise
- Biochemical effects in animals
- Advanced Glycation End Products research
- Advanced Fluorescence Microscopy Techniques
- Gastrointestinal motility and disorders
- Mesenchymal stem cell research
- Heart Rate Variability and Autonomic Control
- Biomedical Ethics and Regulation
- Gastrointestinal Bleeding Diagnosis and Treatment
- Fuel Cells and Related Materials
- Social Robot Interaction and HRI
Osaka University
2015-2025
Takeda (Japan)
2015-2023
Takeda (United States)
2022
Tokushima University
2017
Kindai University
2006-2007
Ibaraki University
2005
Osaka Dental University
1968
An in vitro drug-induced cardiotoxicity assay is a critical step drug discovery for clinical use. The use of human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) promising this purpose. However, single hiPSC-CMs are limited their ability to mimic native cardiac tissue structurally and functionally, the generation artificial using an ongoing challenging. We therefore developed new method constructing three-dimensional (3D) tissues short time by coating extracellular matrix...
Despite major therapeutic advances, heart failure, as a non-communicable disease, remains life-threatening disorder, with 26 million patients worldwide, causing more deaths than cancer. Therefore, novel strategies for the treatment of failure continue to be an important clinical need. Based on preclinical studies, allogenic human induced pluripotent stem cell-derived cardiomyocyte (hiPSC-CM) patches have been proposed potential candidate failure. We report implantation allogeneic hiPSC-CM in...
Abstract Background Cell- or tissue-based regenerative therapy is an attractive approach to treat heart failure. A tissue patch that can safely and effectively repair damaged muscle would greatly improve outcomes for patients with In this study, we conducted a preclinical proof-of-concept analysis of the efficacy safety clinical-grade human induced pluripotent stem cell-derived cardiomyocyte (hiPSC-CM) patches. Methods hiPSC line was established using peripheral blood mononuclear cells from...
Although engineered cardiac tissues (ECTs) derived from induced pluripotent stem cells (iPSCs) are promising for myocardial regenerative therapy, the appropriate ratio of cardiomyocytes to non-cardiomyocytes is not fully understood. Here, we determined whether ECT-cell content a key determinant its structure/function, thereby affecting ECT therapeutic potential advanced heart failure. Scaffold-free ECTs containing different ratios (25%, 50%, 70%, or 90%) iPSC-derived were generated by...
With the expected increase in patients with heart failure and ischemic 15 cardiomyopathy, development of myocardial regenerative medicine using cell transplantation as a novel treatment method is progressing. This first-in-human clinical trial aimed to confirm safety cardiomyocyte patch derived from allogeneic induced pluripotent stem (iPS) cells based on results several preclinical studies.The inclusion criteria were left ventricular ejection fraction 35% or less; symptoms New York Heart...
Abstract Transplantation of cardiomyocytes (CMs) derived from human induced pluripotent stem cells (hiPSC-CMs) is a promising treatment for heart failure, but residual undifferentiated hiPSCs and malignant transformed may lead to tumor formation. Here we describe highly sensitive tumorigenicity assay the detection these in hiPSC-CMs. The soft agar colony formation cell growth analysis were unable detect malignantly There no karyotypic abnormalities during subculture differentiation. hiPSC...
Stem cell-secreted extracellular vesicles (EVs) play essential roles in intercellular communication and restore cardiac function animal models of ischemic heart disease. However, few studies have used EVs derived from clinical-grade stem cells their derivatives with stable quality. Moreover, there is little information on the mechanism time course multifactorial effect EV therapy acute to chronic phase, affected cells, whether effects are direct or indirect.
Abstract Background In Crohn’s disease (CD), the active phase is characterized by lymphatic edema, mesenteric thickening, and enlarged lymph nodes (MLNs). Numerous lymphoid follicle-like structures are observed in inflamed areas, suggesting that follicles germinal centers play critical roles CD pathogenesis. Surgical resection including thickened mesentery may reduce recurrence; however, role of MLNs remains unclear. BACH2, a key regulator center B-cell function, was analyzed to clarify its...
Loss-of-function mutations in PKP2, which encodes plakophilin-2, cause arrhythmogenic cardiomyopathy (AC). Restoration of deficient molecules can serve as upstream therapy, thereby requiring a human model that recapitulates disease pathology and provides distinct readouts phenotypic analysis for proof concept gene replacement therapy. Here, we generated isogenic induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) with precisely adjusted expression plakophilin-2 from patient AC...
Abstract Desmoglein-2, encoded by DSG2, is one of the desmosome proteins that maintain structural integrity tissues, including heart. Genetic mutations in DSG2 cause arrhythmogenic cardiomyopathy, mainly an autosomal dominant manner. Here, we identified a homozygous stop-gain (c.C355T, p.R119X) led to complete desmoglein-2 deficiency patient with severe biventricular heart failure. Histological analysis revealed abnormal deposition proteins, disrupted intercalated disk structures myocardium....
The role of nitric oxide in the development selenite-induced cataracts rats was examined using synthase (NOS) inhibitors.Subcutaneous injection sodium selenite used to induce rats, with or without pretreatment NOS inhibitors. anterior eye segment analysis system (EAS-1000, Nidek) measure lens opacity. glutathione content lenses determined by an HPLC method and Ca2+ atomic absorption spectrometry. Nitrite, a stable metabolite oxide, fluorometrically. NADPH-diaphorase activity staining Western...
Estimation of dynamic change crossbridge formation in living cardiomyocytes is expected to provide crucial information for elucidating cardiomyopathy mechanisms, efficacy an intervention, and others. Here, we established assay system dynamically measure second harmonic generation (SHG) anisotropy derived from myosin filaments depended on their status pulsating cardiomyocytes. Experiments utilizing inheritable mutation that induces excessive myosin-actin interactions revealed the correlation...
Abstract Research on cardiomyopathy models using engineered heart tissue (EHT) created from disease‐specific induced pluripotent stem cells (iPSCs) is advancing rapidly. However, the study of restrictive (RCM), a rare and intractable cardiomyopathy, remains at experimental stage because there currently no established method to replicate hallmark phenotype RCM, particularly diastolic dysfunction, in vitro. In this study, we generated iPSCs patient with early childhood‐onset RCM harboring...
Human iPSC-derived cardiomyocytes (hiPSC-CMs) exhibit functional immaturity, potentially impacting their suitability for assessing drug proarrhythmic potential. We previously devised a traveling wave (TW) system to promote maturation in 3D cardiac tissue. To align with current assessment paradigms (CiPA and JiCSA), necessitating 2D monolayer tissue, we integrated the TW multi-electrode array. This gave rise hiPSC-derived closed-loop tissue (iCT), enabling spontaneous initiation swift pacing...
Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) are used for cardiac safety assessment but have limitations the evaluation of drug-induced contractility. Three-dimensional (3D) tissues similar to native tissue and valuable However, a longer time specialized equipment required generate 3D tissues. We previously developed simple method in short period by coating cell surfaces with extracellular matrix proteins. hypothesized that this could be simultaneous repolarization...
Abstract We hypothesized that an appropriate ratio of cardiomyocytes, fibroblasts, endothelial cells, and extracellular matrix (ECM) factors would be required for the development three-dimensional cardiac tissues (3D-CTs) as drug screening systems. To verify this hypothesis, ECM-coated human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs), fibroblasts (CFs), uncoated cells (CEs) were mixed in following ratios: 10:0:0 (10CT), 7:2:1 (7CT), 5:4:1 (5CT), 2:7:1 (2CT). The...
Background Clinical effectiveness of autologous skeletal cell-patch implantation for nonischemic dilated cardiomyopathy has not been clearly elucidated in clinical settings. This study aimed to determine the feasibility, safety, therapeutic efficacy, and predictor responders this treatment patients with cardiomyopathy. Methods Results Twenty-four left ventricular ejection fraction <35% on optimal medical therapy were enrolled. Autologous cell patches implanted over surface ventricle through...
Abstract Background Despite major therapeutic advances, heart failure remains a life-threatening disorder, with 26 million patients worldwide, causing more deaths than cancer as non-communicable disease. Therefore, novel strategies for the treatment of continue to be an important clinical need. Based on preclinical studies, allogenic human-induced pluripotent stem cell-derived cardiomyocyte (hiPSC-CM) patches have been proposed potential candidate failure. We report implantation allogeneic...
Background: The Δ160E mutation in TNNT2 , which encodes troponin T, is a rare pathogenic variant identified patients with hypertrophic cardiomyopathy and associated poor prognosis. Thus, convenient human model recapitulating the pathological phenotype caused by required for therapeutic development. Methods: We heterozygous in-frame deletion (c.478_480del, p.Δ160E) patient familial showing progressive left ventricular systolic dysfunction, leading to advanced heart failure. To investigate...
In this study, we attempted to enhance disulfiram (DSF) solubility using a 2-hydroxypropyl-beta-cyclodextrin (HPbetaCD) and hydroxypropylmethylcellulose (HPMC). We also investigated the effect of an HPbetaCD solution containing DSF HPMC (DSF eye drops) on cataract development in ICR/f rat. The increased with increasing concentration, 0.1% was approximately 20% greater than that without HPMC. vivo transcorneal penetration experiments rabbits, only diethyldithiocarbamate (DDC) detected not...
Background Extracellular matrix, especially laminin‐221, may play crucial roles in viability and survival of human‐induced pluripotent stem cell‐derived cardiomyocytes (hiPS‐CMs) after vivo transplant. Then, we hypothesized laminin‐221 have an adjuvant effect on therapeutic efficacy by enhancing cell transplantation 3‐dimensional engineered cardiac tissue (ECT) to a rat model myocardial infarction. Methods Results In vitro study indicates the impacts hiPS‐CMs were analyzed basis mechanical...