A5006432524- Pancreatic function and diabetes
- Pluripotent Stem Cells Research
- CRISPR and Genetic Engineering
- Congenital heart defects research
- Tissue Engineering and Regenerative Medicine
- 3D Printing in Biomedical Research
- Renal and related cancers
- Diabetes and associated disorders
- Cannabis and Cannabinoid Research
- Genetics and Neurodevelopmental Disorders
- Liver physiology and pathology
- Diabetes Management and Research
- Drug Transport and Resistance Mechanisms
- Liver Disease Diagnosis and Treatment
- Diet and metabolism studies
- Pharmacological Effects and Toxicity Studies
- Dialysis and Renal Disease Management
- Birth, Development, and Health
- Epigenetics and DNA Methylation
- HIV/AIDS drug development and treatment
- Pancreatic and Hepatic Oncology Research
- Metabolism, Diabetes, and Cancer
- Amino Acid Enzymes and Metabolism
- Cancer Research and Treatments
- Amyloidosis: Diagnosis, Treatment, Outcomes
Tokyo Institute of Technology
2015-2024
Institute of Science Tokyo
2024
Kumamoto University
2005-2017
Hiroshima University Hospital
2013
Kumamoto University Hospital
2000-2002
Miyazaki Welfare Medical College
2001
We recently reported a novel method to induce embryonic stem (ES) cells differentiate into an endodermal fate, especially pancreatic, using supporting cell line. Here we describe the modified culture condition with addition and withdrawal of secreted growth factors could ES selectively hepatic fate efficiently. The signaling BMP FGF that have been implicated in differentiation during normal development are shown play pivotal roles generating from definitive endoderm derived cells. Moreover,...
Abstract The generation of specific lineages the definitive endoderm from embryonic stem (ES) cells is an important issue in developmental biology, as well regenerative medicine. This study demonstrates that ES are induced sequentially into regional-specific gut lineages, such pancreatic, hepatic, and other cell when they cultured directly on a monolayer mesoderm-derived supporting cells. A detailed chronological analysis revealed Activin, fibroblast growth factor, or bone morphogenetic...
Abstract The studies of differentiation mouse or human embryonic stem cells (hESCs) into specific cell types the intestinal would provide insights to understanding development and ultimately yield for use in future regenerative medicine. Here, using an vitro procedure pluripotent definitive endoderm (DE), inductive signal pathways' guiding was investigated. We found that activation Wnt/β-catenin inhibition Notch signaling pathways, by simultaneous application 6-bromoindirubin-3′-oxime (BIO),...
Abstract The small intestine and liver play important role in determining oral drug's fate. Both organs are also interconnected through enterohepatic circulation, which imply there crosstalk circulating factors such as signaling molecules or metabolites that may affect drug metabolism. Coculture of hepatocytes intestinal cells have shown to increase hepatic metabolism, yet its mechanism is still unclear. In this study, we aim elucidate by coculturing primary human harvested from chimeric...
Epigenetic regulation is essential in determining cellular phenotypes during differentiation. Although tissue-specific DNA methylation has been studied, the significance of variance for tissue remains unresolved, especially CpG-poor promoters. Here, we comprehensively studied levels 27 578 CpG sites among 21 human normal tissues from 12 anatomically different regions using an epigenotyping beadarray system. Remarkable changes were observed within promoters but not CpG-rich Of note,...
Human induced pluripotent stem (hiPS) cells are considered a potential source for the generation of insulin-producing pancreatic β-cells because their differentiation capacity. In this study, we have developed five-step xeno-free culture system to efficiently differentiate hiPS into in vitro. We found that high NOGGIN concentration is crucial specifically inducing first and duodenal homeobox-1 (PDX1)-positive progenitors then neurogenin 3 (NGN3)-expressing endocrine progenitors, while...
We previously reported that embryonic stem (ES) cells cultured on M15 cells, a mesoderm-derived supportive cell line, were efficiently differentiated towards an endodermal fate, finally adopting the specific lineages of various digestive organs such as pancreas and liver. show here endoderm-inducing activity is in part mediated through extracellular matrices, laminin α5 one crucial components. In attempt to establish feeder-free ES-cell procedure for pancreatic differentiation, we used...
The endoderm-inducing effect of the mesoderm-derived supportive cell line M15 on embryonic stem (ES) cells is partly mediated through extracellular matrix, which laminin α5 a crucial component. Mouse ES or induced pluripotent cultured synthesized basement membrane (sBM) substratum, using an HEK293 (rLN10-293 cell) stably expressing laminin-511, could differentiate into definitive endoderm and subsequently pancreatic lineages. In this study, we investigated differentiation sBM mouse human...
Embryogenesis is tightly regulated by multiple levels of epigenetic regulation such as DNA methylation, histone modification, and chromatin remodeling. methylation patterns are erased in primordial germ cells the interval immediately following fertilization. Subsequent developmental reprogramming occurs de novo demethylation. Variance between different cell types not well understood. Here, using methylated immunoprecipitation tiling array technology, we have comprehensively analyzed at...
Implantable pancreatic β cell-encapsulated devices are required for the treatment of type 1 diabetes. Such should enable a semipermeable membrane to release insulin in response glucose levels while avoiding immune reactions. Micrometer-thick track-etched porous polycarbonate (PC) membranes have been used this purpose. However, immediate remains challenge development such membranes. Herein, we attempted develop freestanding polymeric ultrathin film (nanosheet) with structure that can be...
Abstract Examining intestine–liver interactions is important for achieving the desired physiological drug absorption and metabolism response in vitro tests. Multi-organ microphysiological systems (MPSs) constitute promising tools evaluating inter-organ vitro. For coculture on MPSs, normal cells are challenging to use because they require complex maintenance careful handling. Herein, we demonstrated potential of coculturing MPSs evaluation interactions. To this end, cocultured human-induced...
We aimed to establish an in vitro differentiation procedure generate matured small intestinal cells mimicking human intestine from human-induced pluripotent stem (iPSCs). previously reported the efficient generation of CDX2-expressing progenitor embryonic (ESCs) using 6-bromoindirubin-3′-oxime (BIO) and (3,5-difluorophenylacetyl)-L-alanyl-L-2-phenylglycine tert-butyl ester (DAPT) treat definitive endodermal cells. Here, we demonstrate enterocyte-like by culturing iPSC-derived on a collagen...
Epiplakin1 (Eppk1) is a plakin family gene with its function remains largely unknown, although the genes are known to in interconnecting cytoskeletal filaments and anchoring them at plasma membrane‐associated adhesive junction. Here we analyzed expression patterns of Eppk1 developing adult pancreas mice. In embryonic pancreas, Eppk1+/Pdx1+ Eppk1+/Sox9+ pancreatic progenitor cells were observed early epithelium. Since Pdx1 overlapped that Sox9 this stage, these multipotent Eppk1+/Pdx1+/Sox9+...
Embryonic stem (ES) cells recapitulate normal developmental processes and serve as an attractive source for routine access to a large number of research therapies. We previously reported that ES cultured on M15 cells, or synthesized basement membrane (sBM) substratum, efficiently differentiated into endodermal fate subsequently adopted fates various digestive organs, such the pancreas liver. Here, we established novel hepatic differentiation procedure using synthetic nanofiber (sNF) cell...
Understanding the molecular mechanisms that regulate β cell mass and proliferation is important for treatment of diabetes. Here, we identified domperidone (DPD), a dopamine D2 receptor (DRD2) antagonist enhances mass. Over time, islet loss occurs in dissociation cultures, this was inhibited by DPD. DPD increased decreased apoptosis cells through increasing intracellular cAMP. prevented dedifferentiation, which together highly contributed to DRD2 knockdown phenocopied effects number cells....
Abstract Embryonic stem (ES) and induced pluripotent (iPS) cells have potential applications to regenerative medicine for diabetes; however, a useful safe way generate pancreatic β has not been developed. In this study, we tried establish an effective method of differentiation through the protein transduction three transcription factors (Pdx1, NeuroD, MafA) important cell development. The poses no risk unexpected genetic modifications in target cells. Transduction proteins mouse ES iPS into...