Publications by authors named "Fumiya Tokito"

Article Synopsis
  • The study focuses on different subtypes of pancreatic β-cells that regulate insulin secretion and glucose balance, using 3D spheroids derived from human induced pluripotent stem cells (hiPSCs) to mimic these β-cell subtypes and islet-like structures.
  • Researchers examined the signaling patterns of transcription regulators (TRs) in β-cell subpopulations through a systematic analysis of existing single-cell sequencing data, identifying key regulatory networks for these cells.
  • The findings highlight the diversity among β-cell subtypes and propose mechanisms behind their differentiation, which could be crucial for understanding how imbalances in these subtypes contribute to insulin secretion issues in type 2 diabetes.
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Type 2 diabetes (T2D) is posing a serious public health concern with a considerable impact on human life and health expenditures worldwide. The disease develops when insulin plasma level is insufficient for coping insulin resistance, caused by the decline of pancreatic β-cell function and mass. In β-cells, the lipotoxicity exerted by saturated free fatty acids in particular palmitate (PA), which is chronically elevated in T2D, plays a major role in β-cell dysfunction and mass.

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Article Synopsis
  • Estimating how drugs and their metabolites are cleared from bile is essential for understanding liver function and possible interactions between drugs in humans.
  • Researchers explored a new way to analyze bile by coculturing human liver cancer cells (HepG2-NIAS) and cholangiocarcinoma cells (TFK-1) using a special membrane, which improved drug permeability compared to using only HepG2-NIAS cells.
  • The coculture not only increased the recovery of bile compounds without damaging cell structures, but also highlighted a promising method for more effective drug analysis in the lab.
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Recent advancements in bioengineering have introduced potential alternatives to liver transplantation via the development of self-assembled liver organoids, derived from human-induced pluripotent stem cells (hiPSCs). However, the limited maturity of the tissue makes it challenging to implement this technology on a large scale in clinical settings. In this study, we developed a highly efficient method for generating functional liver organoids from hiPSC-derived carboxypeptidase M liver progenitor cells (CPM+ LPCs), using a microwell structure, and enhanced maturation through direct oxygenation in oxygen-permeable culture plates.

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Correction for 'Generation of β-like cell subtypes from differentiated human induced pluripotent stem cells in 3D spheroids' by Lisa Morisseau , , 2023, https://doi.org/10.1039/d3mo00050h.

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Since the identification of four different pancreatic β-cell subtypes and bi-hormomal cells playing a role in the diabetes pathogenesis, the search for models that mimics such cells heterogeneity became a key priority in experimental and clinical diabetology. We investigated the potential of human induced pluripotent stem cells to lead to the development of the different β-cells subtypes in honeycomb microwell-based 3D spheroids. The glucose-stimulated insulin secretion confirmed the spheroids functionality.

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Functional differentiation of pancreatic like tissue from human induced pluripotent stem cells is one of the emerging strategies to achieve an pancreas model. Here, we propose a protocol to cultivate hiPSC-derived β-like-cells coupling spheroids and microfluidic technologies to improve the pancreatic lineage maturation. The protocol led to the development of spheroids producing the C-peptide and containing cells positive to insulin and glucagon.

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Article Synopsis
  • Primary cultured hepatocytes are essential for studying liver metabolism and toxicity, but they often lose function after isolation due to an unnatural environment.
  • Polydimethylsiloxane (PDMS) enhances hepatocyte function due to its high oxygen permeability, but its tendency to absorb chemicals has limited its application in drug development.
  • A new material, 4-polymethyl-1-pentene polymer (PMP), maintains liver function effectively for at least a week and shows promise as a superior alternative to PDMS and traditional polystyrene for drug testing.
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The liver plays a pivotal role in the clearance of drugs. Reliable assays for liver function are crucial for various metabolism investigation, including toxicity, disease, and pre-clinical testing for drug development. Bile is an aqueous secretion of a functioning liver.

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In situ continuous glucose monitoring under physiological culture conditions is imperative in understanding the dynamics of cell and tissue behaviors and their physiological responses since glucose plays an important role in principal source of biological energy. We therefore examined physiologically relevant dynamic changes in glucose levels based on glucose metabolism and production during aerobic culture (10% O) of rat primary hepatocytes stimulated with insulin or glucagon on a highly O permeable plate, which can maintain the oxygen concentration close to the periportal zone of the liver. As glucose monitoring devices, we used oxygen-independent glucose dehydrogenase-modified single-walled carbon nanotube electrodes placed close to the surface of the hepatocytes.

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Transplantation of macroencapsulated pancreatic islets within semipermeable membranes is a promising approach for the treatment of type 1 diabetes. Encapsulation beneficially isolates the implants from the host immune system. Deleteriously however, it also limits oxygen supply to the cells.

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