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Related Concept Videos

iPS Cell Differentiation01:22

iPS Cell Differentiation

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The ability of induced pluripotent stem cells or iPSCs to differentiate into most body cell types has stimulated repair and regenerative medicine research over the past few decades. iPSC-derived blood cells, hepatocytes, beta islet cells, cardiomyocytes, neurons, and other cell types can repair injuries or regenerate damaged tissue in diseases such as diabetes and neurodegenerative disorders.
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EPS and iPS Cells in Disease Research01:21

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Embryonic and induced pluripotent stem cells are excellent models for disease research because of their ability to self-renew and differentiate into most cell types. Somatic cells from a patient are isolated and reprogrammed into induced pluripotent stem cells or iPSCs. These iPSCs are later differentiated into the desired cell type, which mirrors the diseased cell of the patient. In this way, disease models have been created for investigating diseases such as Down syndrome, type I diabetes,...
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Somatic to iPS Cell Reprogramming01:29

Somatic to iPS Cell Reprogramming

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Reprogramming alters the gene expression in somatic cells, transforming them into induced pluripotent stem (iPS) cells over several generations. Scientists can reprogram cells by introducing genes for four transcription factors—Oct4, Sox2, Klf4, and c-Myc (OSKM) by viral or non-viral methods. These factors are also known as Yamanaka factors after Shinya Yamanaka, who first generated iPS cells using mouse skin cells. Yamanaka was awarded the Nobel Prize in Physiology or Medicine in 2012...
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Chromatin Modification in iPS Cells01:32

Chromatin Modification in iPS Cells

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Chromatin modification alters gene expression; therefore, scientists can add histone-modifying enzymes, histone variants, and chromatin remodeling complexes to somatic cells to aid reprogramming into pluripotent stem (iPS) cells.
Compact chromatin makes reprogramming difficult. Enzymes, such as histone demethylases and acetyltransferases, are often added during reprogramming to loosen the chromatin, making the DNA more accessible to transcription factors. Molecules that inhibit histone...
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B Cell Activation and Differentiation01:24

B Cell Activation and Differentiation

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The adaptive immune response, a sophisticated defense mechanism, relies on the activation and differentiation of B lymphocytes, or B cells. These processes enable our bodies to mount a tailored response against specific pathogens such as bacteria, free virus particles, toxins, and parasites.
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Effect of Hepatic Disease on Pharmacokinetics: Dose Adjustments Due to Hepatic Impairment01:08

Effect of Hepatic Disease on Pharmacokinetics: Dose Adjustments Due to Hepatic Impairment

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Hepatic impairment, characterized by decreased liver function, does not uniformly mandate adjustments in drug dosage. Whether dosage modifications are necessary depends on various factors related to the drug's metabolism and elimination pathways. If a drug is primarily excreted via the kidneys and bypasses significant hepatic processing, if it undergoes minimal metabolic transformation in the liver, or if it is volatile and primarily expelled through the lungs, dose adjustments may not be...
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Efficient Neural Differentiation using Single-Cell Culture of Human Embryonic Stem Cells
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Optimal human iPS cell culture method for efficient hepatic differentiation.

Nobumasa Matoba1, Tomoki Yamashita1, Kazuo Takayama2

  • 1Laboratory of Biochemistry and Molecular Biology, Graduate School of Pharmaceutical Sciences, Osaka University, Osaka 565-0871, Japan.

Differentiation; Research in Biological Diversity
|October 2, 2018
PubMed
Summary

Human induced pluripotent stem cell (iPSC) maintenance significantly impacts hepatic differentiation. The feeder cell method using mouse embryonic fibroblasts yielded superior hepatocyte-like cells compared to feeder-free methods.

Keywords:
DifferentiationHepatocyteHuman induced pluripotent stem cellsiPS maintenance method

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Area of Science:

  • Stem cell biology
  • Hepatocyte differentiation
  • Regenerative medicine

Background:

  • Human induced pluripotent stem cells (iPSCs) hold promise for pharmaceutical research and regenerative medicine.
  • Effective differentiation into hepatocyte-like cells is crucial for these applications.
  • The influence of iPSC maintenance methods on hepatic differentiation potential remains unclear.

Purpose of the Study:

  • To investigate how different human iPSC maintenance methods affect subsequent hepatic differentiation.
  • To identify the optimal iPSC culture conditions for efficient generation of functional hepatocyte-like cells.

Main Methods:

  • Human iPSCs were cultured using four distinct methods: ReproStem with feeder cells, AK02N with iMatrix-511, Essential 8 with Vitronectin N, and TeSR-E8 with Vitronectin XF.
  • These cultured iPSCs were then differentiated into hepatocyte-like cells.
  • Gene expression of definitive endoderm and foregut markers, as well as hepatocyte markers (albumin, urea secretion, CYP3A4 activity), were analyzed.

Main Results:

  • Higher expression of definitive endoderm markers was observed in iPSCs cultured with ReproStem or TeSR-E8 medium.
  • The ReproStem medium with feeder cells resulted in elevated HHEX (foregut marker) expression.
  • Significantly higher expression of hepatocyte markers (albumin, urea secretion capacity, CYP3A4 activity) was achieved using the ReproStem method with feeder cells.

Conclusions:

  • The choice of human iPSC maintenance method critically influences hepatic differentiation efficiency.
  • The on-feeder method using mouse embryonic fibroblasts is superior to feeder-free methods for generating functional hepatocyte-like cells from human iPSCs.
  • This finding is vital for optimizing protocols in stem cell-based drug discovery and regenerative therapies.