A5079661753- Pluripotent Stem Cells Research
- CRISPR and Genetic Engineering
- Tissue Engineering and Regenerative Medicine
- Congenital heart defects research
- RNA Interference and Gene Delivery
- Neuroscience and Neural Engineering
- Cardiomyopathy and Myosin Studies
- Cardiac Fibrosis and Remodeling
- RNA Research and Splicing
- Fuel Cells and Related Materials
- Hippo pathway signaling and YAP/TAZ
- Radiation Effects in Electronics
- Atherosclerosis and Cardiovascular Diseases
- Wound Healing and Treatments
- Vascular anomalies and interventions
- Advanced Proteomics Techniques and Applications
- Cardiovascular Function and Risk Factors
- Mass Spectrometry Techniques and Applications
- Adipose Tissue and Metabolism
- Angiogenesis and VEGF in Cancer
- Viral Infections and Immunology Research
- Cell Adhesion Molecules Research
- Mesenchymal stem cell research
- Central Venous Catheters and Hemodialysis
- Advanced MRI Techniques and Applications
University of Washington
2019-2024
Keio University Hospital
2015-2023
Keio University
2011-2020
Japan Science and Technology Agency
2015
Cardiovascular Research Center
2013
Nippon Medical School
2012
RIKEN BioResource Research Center
2012
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...
BACKGROUND: Metabolic remodeling and mitochondrial dysfunction are hallmarks of heart failure with reduced ejection fraction. However, their role in the pathogenesis HF preserved fraction (HFpEF) is poorly understood. METHODS: In a mouse model HFpEF, induced by high-fat diet Nω-nitrol-arginine methyl ester, cardiac energetics was measured 31 P NMR spectroscopy substrate oxidation profile assessed 13 C-isotopmer analysis. Mitochondrial functions were tissue human pluripotent stem cell–derived...
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...
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...
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...
Abstract In deep burns, early wound closure is important for healing, and skin grafting mainly used closure. However, it difficult to achieve in extensive total body surface area burns due the lack of donor sites. Dermal fibroblasts, responsible dermis formation, may be lost burns. fat layers composed adipocytes, lying underneath dermis, are retained even such cases. Direct reprogramming a novel method directly reprograming some cells into other types by introducing specific master...
are widely used for drug delivery to target specific organs with enhanced vascular permeability.Since permeability would be observed in myocarditis hearts due severe inflammation, we hypothesized that immunosuppressive agent encapsulated liposomes enhance its therapeutic effects.In this study, have prepared polyethylene glycol-modified encapsulating FK506 (liposomal FK506) (4109 nm) and examined effects rat model of experimental autoimmune (EAM) which Lewis rats were sensitized porcine...