A5083622539- Pluripotent Stem Cells Research
- Tissue Engineering and Regenerative Medicine
- CRISPR and Genetic Engineering
- Congenital heart defects research
- Cardiac Fibrosis and Remodeling
- RNA Interference and Gene Delivery
- Viral Infections and Immunology Research
- Signaling Pathways in Disease
- Hippo pathway signaling and YAP/TAZ
- Virus-based gene therapy research
- Neuroscience and Neural Engineering
- Non-Invasive Vital Sign Monitoring
- Pulmonary Hypertension Research and Treatments
- Muscle Physiology and Disorders
- Cell Adhesion Molecules Research
- Electrospun Nanofibers in Biomedical Applications
- Biomedical and Engineering Education
- Atherosclerosis and Cardiovascular Diseases
- Amyloidosis: Diagnosis, Treatment, Outcomes
- Eosinophilic Disorders and Syndromes
- Protease and Inhibitor Mechanisms
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- 3D Printing in Biomedical Research
- Neurological and metabolic disorders
- Cardiac Arrhythmias and Treatments
Keio University
2012-2024
Keio University Hospital
2015-2024
University of Tsukuba
2018-2023
Gladstone Institutes
2015
Kyoto University
2015
Japan Science and Technology Agency
2015
RIKEN BioResource Research Center
2012
Nippon Medical School
2012
Saiseikai Central Hospital
2009
Heart disease remains a leading cause of death worldwide. Owing to the limited regenerative capacity heart tissue, cardiac therapy has emerged as an attractive approach. Direct reprogramming human fibroblasts (HCFs) into cardiomyocytes may hold great potential for this purpose. We reported previously that induced cardiomyocyte-like cells (iCMs) can be directly generated from mouse in vitro and vivo by transduction three transcription factors: Gata4, Mef2c, Tbx5, collectively termed GMT. In...
After myocardial infarction (MI), massive cell death in the myocardium initiates fibrosis and scar formation, leading to heart failure. We recently found that a combination of 3 cardiac transcription factors, Gata4, Mef2c, Tbx5 (GMT), reprograms fibroblasts directly into functional cardiomyocytes vitro.To investigate whether viral gene transfer GMT infarcted hearts induces cardiomyocyte generation.Coronary artery ligation was used generate MI mouse. In vitro transduction retrovirus converted...
Fibroblasts can be directly reprogrammed into cardiomyocyte-like cells (iCMs) by overexpression of cardiac transcription factors, including Gata4, Mef2c, and Tbx5; however, this process is inefficient under serum-based culture conditions, in which conversion partially fully functional iCMs has been a major hurdle. Here, we report that combination fibroblast growth factor (FGF) 2, FGF10, vascular endothelial (VEGF), termed FFV, promoted reprogramming defined serum-free increasing...
Abstract Direct cardiac reprogramming from fibroblasts can be a promising approach for disease modeling, drug screening, and regeneration in pediatric adult patients. However, postnatal are less efficient compared with embryonic fibroblasts, barriers to associated aging remain undetermined. In this study, we screened 8400 chemical compounds found that diclofenac sodium (diclofenac), non-steroidal anti-inflammatory drug, greatly enhanced combination Gata4 , Mef2c Tbx5 (GMT) or GMT plus Hand2...
Because adult cardiomyocytes have little regenerative capacity, resident cardiac fibroblasts (CFs) synthesize extracellular matrix after myocardial infarction (MI) to form fibrosis, leading dysfunction and heart failure. Therapies that can regenerate the myocardium reverse fibrosis in chronic MI are lacking. The overexpression of transcription factors, including Mef2c/Gata4/Tbx5/Hand2 (MGTH), directly reprogram CFs into induced (iCMs) improve function under acute MI. However, ability vivo...
Direct cardiac reprogramming holds great potential for regenerative medicine. However, it remains inefficient, and induced cardiomyocytes (iCMs) generated in vitro are less mature than those vivo, suggesting that undefined extrinsic factors may regulate reprogramming. Previous studies mainly used hard polystyrene dishes, yet the effect of substrate rigidity on unclear. Thus, we developed a Matrigel-based hydrogel culture system to determine roles matrix stiffness mechanotransduction We found...
It has never been possible to immediately evaluate heart rate variability (HRV) during exercise. We aimed visualize the real-time changes in power spectrum of HRV exercise and investigate its relationship ventilatory threshold (VT).Thirty healthy subjects (29.1±5.7 years age) 35 consecutive patients (59.0±13.2 with myocardial infarctions underwent cardiopulmonary tests an RAMP protocol ergometer. The was continuously assessed spectral analyses using maximum entropy method projected on a...
Myoblast determination protein 1 (MyoD) dynamics define the activation status of muscle stem cells (MuSCs), aiding in tissue regeneration after injury. However, lack experimental platforms to monitor MyoD
Cardiac transcription factors (TFs) directly reprogram fibroblasts into induced cardiomyocytes (iCMs), where MEF2C acts as a pioneer factor with GATA4 and TBX5 (GT). However, the generation of functional mature iCMs is inefficient, molecular mechanisms underlying this process remain largely unknown. Here, we found that overexpression transcriptionally activated via fusion powerful MYOD transactivation domain combined GT increased beating by 30-fold. Activated generated were...
The mechanisms underlying pulmonary hypertension (PH) remain largely unknown; further, why advanced vascular remodeling preferentially occurs in arterioles is yet to be answered. VEGF (vascular endothelial growth factor) regulates angiogenesis through Flk1 (fetal liver kinase 1) and Flt1 (fms-like tyrosine on cells (ECs), which may related PH pathogenesis. However, spatiotemporal expression patterns of the system role development poorly understood.We analyzed multiple reporter mice,...
Direct reprogramming is a promising approach in regenerative medicine. Overexpression of the cardiac transcription factors Gata4, Mef2c, and Tbx5 (GMT) or GMT plus Hand2 (GHMT) directly reprogram fibroblasts into cardiomyocyte-like cells (iCMs). However, critical timing transgene expression molecular mechanisms for remain unclear. The conventional doxycycline (Dox)-inducible temporal systems require simultaneous transduction two vectors (pLVX-rtTA/pLVX-cDNA) harboring reverse tetracycline...
Objective Myocardial fibrosis related to non-specific inflammation can be detected using late gadolinium-enhancement cardiovascular MR (LGE-CMR), which is an important prognostic indicator for dilated cardiomyopathy (DCM). The aims of this study were define the factors DCM with LGE-CMR, and evaluate impact on adverse effects. Methods We performed a retrospective analysis prospectively maintained single centre registry. analysed data from 76 patients who had been admitted acute heart failure....