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Related Concept Videos

Phase II Reactions: Methylation Reactions01:17

Phase II Reactions: Methylation Reactions

Methylation is a phase II biotransformation process involving the attachment of a methyl group to a substrate. Enzymes known as methyltransferases orchestrate this reaction.
The mechanism of methylation unfolds in two stages. The first stage sees a methyltransferase enzyme facilitating the transfer of a methyl group from S-adenosylmethionine (SAM) to the substrate, forming S-adenosylhomocysteine (SAH). The second stage involves further metabolism of SAH into homocysteine, which can be recycled...
Pharmacogenetics of Phase II Enzymes: N-acetyltransferase, Thiopurine S-methyltransferase, UDP-glucuronosyltransferase01:27

Pharmacogenetics of Phase II Enzymes: N-acetyltransferase, Thiopurine S-methyltransferase, UDP-glucuronosyltransferase

Phase II biotransformation reactions are essential for detoxifying and eliminating xenobiotics, including many pharmaceutical compounds. These reactions typically involve conjugation, the covalent attachment of polar endogenous groups such as glucuronic acid, sulfate, methyl, or acetyl moieties to functional groups introduced during Phase I metabolism. The resulting conjugates are more water-soluble, enabling efficient renal or biliary excretion.The major classes of Phase II enzymes include...

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LINE-1 Methylation Analysis in Mesenchymal Stem Cells Treated with Osteosarcoma-Derived Extracellular Vesicles
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Decrease of global methylation improves significantly hepatic differentiation of Ad-MSCs: possible future application

C Seeliger1, M Culmes, L Schyschka

  • 1Technical University Munich, MRI, Department of Trauma Surgery, Germany.

Cell Transplantation
|April 18, 2012
PubMed
Summary
This summary is machine-generated.

Researchers generated hepatocyte-like cells from adipose-derived mesenchymal stem cells (Ad-MSCs) for liver disease treatments. These cells show improved metabolic functions and maintain urea metabolism after cryopreservation, suggesting clinical potential for liver support.

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Area of Science:

  • Regenerative Medicine
  • Hepatology
  • Stem Cell Biology

Background:

  • Hepatocyte transplantation is a viable alternative to orthotopic liver transplantation for bridging organ waitlists and treating liver failure.
  • Limited availability of primary human hepatocytes necessitates the development of alternative cell sources.
  • Adipose-derived mesenchymal stem cells (Ad-MSCs) offer a readily available source for generating hepatocyte-like cells.

Purpose of the Study:

  • To generate functional hepatocyte-like cells from Ad-MSCs for clinical applications.
  • To assess the metabolic and enzymatic activities of these generated cells.
  • To evaluate the potential of these cells for treating metabolic liver diseases, particularly urea cycle disorders.

Main Methods:

  • Ad-MSCs were differentiated into hepatocyte-like cells using a four-step protocol involving epigenetic modifiers (5-azacytidine) and growth factors.
  • Metabolic and enzymatic activities (Phase I and II drug metabolism, urea metabolism) were assessed.
  • Gene expression of hepatic markers (CYP enzymes, alpha-fetoprotein, albumin) was analyzed.
  • Cellular function was evaluated before and after cryopreservation.

Main Results:

  • A four-step differentiation protocol significantly enhanced metabolic and enzymatic activities in Ad-MSC-derived cells.
  • Differentiated cells exhibited increased Phase I and Phase II enzyme activities compared to undifferentiated cells.
  • Urea metabolism in generated cells was comparable to primary human hepatocytes and remained stable after six months of cryopreservation.

Conclusions:

  • Ad-MSCs can be differentiated into hepatocyte-like cells with significant functional improvements.
  • These cells demonstrate promising metabolic functions and cryopreservation stability, suitable for clinical applications.
  • The generated cells show potential for treating urea cycle disorders and other metabolic liver diseases.