In vitro directed differentiation of mouse embryonic stem cells into insulin-producing cells

@article{LenQuinto2004InVD,
  title={In vitro directed differentiation of mouse embryonic stem cells into insulin-producing cells},
  author={Trinidad Le{\'o}n-Quinto and J M Jones and Anouchka Skoudy and Mark M. Burcin and Bernat Soria},
  journal={Diabetologia},
  year={2004},
  volume={47},
  pages={1442-1451}
}
Aims/hypothesisWe recently demonstrated that insulin-producing cells derived from embryonic stem cells normalise hyperglycaemia in transplanted diabetic mice. The differentiation and selection procedure, however, was successful in less than 5% of the assays performed. Thus, to improve its effectiveness, new strategies have been developed, which increase the number of islet cells or islet progenitors. MethodsMouse embryonic stem cells transfected with a plasmid containing the Nkx6.1 promoter… Expand
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References

SHOWING 1-10 OF 22 REFERENCES
Insulin-secreting cells derived from embryonic stem cells normalize glycemia in streptozotocin-induced diabetic mice.
TLDR
An insulin-secreting cell clone is obtained from undifferentiated ES cells using a cell-trapping system and opens new possibilities for tissue transplantation in the treatment of type 1 and type 2 diabetes and offers an alternative to gene therapy. Expand
Expression of Pax4 in embryonic stem cells promotes differentiation of nestin-positive progenitor and insulin-producing cells
TLDR
It is concluded that constitutive expression of Pax4 in combination with histotypic cultivation facilitates ES cell differentiation into the pancreatic lineage, which leads to the formation of islet-like spheroid structures that produce increased levels of insulin. Expand
From stem cells to beta cells: new strategies in cell therapy of diabetes mellitus
TLDR
Results show that diabetes could be among the first applications of stem cell therapy, and insulin-secreting cells derived from R1 mouse embryonic stem cells restore blood glucose concentrations to normal when they are transplanted into streptozotocin-induced diabetic animals. Expand
Transforming growth factor (TGF)beta, fibroblast growth factor (FGF) and retinoid signalling pathways promote pancreatic exocrine gene expression in mouse embryonic stem cells.
TLDR
Mouse embryonic stem cells can undergo exocrine pancreatic differentiation with a kinetic pattern of expression reminiscent of pancreas development in vivo and that ES cells can be coaxed to express an acinar phenotype by activation of signalling pathways known to play a role in pancreatic development and differentiation. Expand
Differentiation of Embryonic Stem Cells to Insulin-Secreting Structures Similar to Pancreatic Islets
TLDR
This work generated cells expressing insulin and other pancreatic endocrine hormones from mouse ES cells that self-assemble to form three-dimensional clusters similar in topology to normal pancreatic islets where pancreatic cell types are in close association with neurons. Expand
Nicotinamide is a potent inducer of endocrine differentiation in cultured human fetal pancreatic cells.
TLDR
The results indicate that NIC induces differentiation and maturation of human fetal pancreatic islet cells, and this model should be useful for the study of molecular mechanisms involved in beta cell development. Expand
Effects of eight growth factors on the differentiation of cells derived from human embryonic stem cells.
TLDR
This analysis sets the stage for directing differentiation of human ES cells in culture and indicates that multiple human cell types may be enriched in vitro by specific factors. Expand
Involvement of hepatocyte nuclear factor 3 in endoderm differentiation of embryonic stem cells
TLDR
HNF3alpha and -beta seem to be involved in early endoderm differentiation of ES cells and together with other developmental factors are apparently needed for the induction of the endodermal lineage in vivo. Expand
Regulation of the Pancreatic Islet-Specific GeneBETA2 (neuroD) by Neurogenin 3
TLDR
It is hypothesize that ngn3 is involved in activating the expression of BETA2 at an early stage of islet cell differentiation through the E boxes in theBETA2 promoter. Expand
Transcriptional and Translational Regulation of β-Cell Differentiation Factor Nkx6.1*
TLDR
Dicistronic assays establish that the 5′-UTR region functions as a potent internal ribosomal entry site, providing cell type-specific regulation of translation and provides the specificity of expression required during pancreas development. Expand
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