Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.1.3.9 (glucose-6-phosphatase)
 3,081 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Human embryonic stem cells (hESCs) have enormous potential as a source of cells for cell replacement therapies and as a model for early human development. In this study we examined the differentiating potential of hESCs into hepatocytes in two- and three-dimensional (2D and 3D) culture systems. Embryoid bodies (EBs) were inserted into a collagen scaffold 3D culture system or cultured on collagen-coated dishes and stimulated with exogenous growth factors to induce hepatic histogenesis. Immunofluorescence analysis revealed the expression of albumin (ALB) and cytokeratin-18 (CK-18). The differentiated cells in 2D and 3D culture system displayed several characteristics of hepatocytes, including expression of transthyretin, alpha-1-antitrypsin, cytokeratin 8, 18, 19, tryptophan-2,3-dioxygenase, tyrosine aminotransferase, glucose-6-phosphatase (G6P), cytochrome P450 subunits 7a1 and secretion of alpha-fetoprotein (AFP) and ALB and production of urea. In 3D culture, ALB and G6P were detected earlier and higher levels of urea and AFP were produced, when compared with 2D culture. Electron microscopy of differentiated hESCs showed hepatocyte-like ultrastructure, including glycogon granules, well-developed Golgi apparatuses, rough and smooth endoplasmic reticuli and intercellular canaliculi. The differentiation of hESCs into hepatocyte-like cells within 3D collagen scaffolds containing exogenous growth factors, gives rise to cells displaying morphological features, gene expression patterns and metabolic activities characteristic of hepatocytes and may provide a source of differentiated cells for treatment of liver diseases.
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PMID:Differentiation of human embryonic stem cells into hepatocytes in 2D and 3D culture systems in vitro. 1689 78

Mesenchymal stem cells are believed to be involved in the formation of mesenchymal tissues, including bone, cartilage, muscle, tendon and adipose tissue. Interestingly, it has previously been reported that mesenchymal stem cells could also differentiate into endoderm-derived cells, such as hepatocytes. The amniotic membrane contains mesenchymal cells and is a readily available human tissue. Therefore, we investigated the potential of mesenchymal cells derived from human amniotic membrane (MC-HAM) to differentiate into hepatocytes. We analyzed the expression of hepatocyte-specific genes in MC-HAM before and after induction of differentiation into hepatocytes. We observed the expression of mRNAs encoding albumin, a-fetoprotein, cytokeratin 18 and alpha1-antitrypsin, but not those encoding glucose-6-phosphatase or ornithine transcarbamylase, prior to the induction of differentiation. However, immunocytochemistry revealed that albumin and alpha-fetoprotein were abundantly produced only after the induction of differentiation into hepatocytes. In addition, we observed the storage of glycogen, a characteristic feature of hepatocytes, using periodic acid-Schiff staining of MC-HAM induced to differentiate into hepatocytes. Overall, MC-HAM appear to be able to differentiate into cells possessing some characteristics of hepatocytes. Although further studies should be carried out to determine whether such in vitro-differentiated cells can function in vivo as hepatocytes. These cells may be useful in various applications that require human hepatocytes.
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PMID:Differentiation of mesenchymal cells derived from human amniotic membranes into hepatocyte-like cells in vitro. 1764 27

Both mature and stem cell-derived hepatocytes lost their phenotype and functionality under conventional culture conditions. However, the 3D scaffolds containing the main extracellular matrix constitutions, such as heparin, may provide appropriate microenvironment for hepatocytes to be functional. The current study aimed to investigate the efficacy of the differentiation capability of hepatocytes derived from human Wharton's jelly mesenchymal stem cells (WJ-MSCs) in 3D heparinized scaffold. In this case, the human WJ-MSCs were cultured on the heparinized and non-heparinized 2D collagen gels or within 3D scaffolds in the presence of hepatogenic medium. Immunostaining was performed for anti-alpha fetoprotein, cytokeratin-18 and -19 antibodies. RT-PCR was performed for detection of hepatic nuclear factor-4 (HNF-4), albumin, cytokeratin-18 and -19, glucose-6-phosphatase (G6P), c-met and Cyp2B. The results indicated that hepatogenic media induced the cells to express early liver-specific markers including HNF4, albumin, cytokeratin-18 and 19 in all conditions. The cells cultured on both heparinized culture conditions expressed late liver-specific markers such as G6P and Cyp2B as well. Besides, the hepatocytes differentiated in 3D heparinized scaffolds stored more glycogen that indicated they were more functional. Non-heparinized 2D gel was the superior condition for cholangiocyte differentiation as indicated by higher levels of cytokeratin 19 expression. In conclusion, the heparinized 3D scaffolds provided a microenvironment to mimic Disse space. Therefore, 3D heparinized collagen scaffold can be suggested as a good vehicle for hepatocyte differentiation.
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PMID:Heparin/Collagen 3D Scaffold Accelerates Hepatocyte Differentiation of Wharton's Jelly-Derived Mesenchymal Stem Cells. 3060