Drug Screening Using Islet Cells and Islet Cell Progenitors from Human Embryonic Stem Cells
This disclosure provides a system for producing pancreatic islet cells from embryonic stem cells. Differentiation is initiated towards endoderm cells, and focused using reagents that promote emergence of islet precursors and mature insulin-secreting cells. High quality populations of islet cells can be produced in commercial quantities for use in research, drug screening, or regenerative medicine.
1 . A method of screening a factor chosen from a drug, a solvent, a peptide and a polynucleotide for its effect on a primate pancreatic islet cell precursor expressing Sox 17 comprising
a) contacting a cell culture of primate pancreatic islet cells precursors expressing Sox 17 with a factor;
b) observing a change in the primate pancreatic islet cell precursor expressing Sox 17 after a); and
c) correlating the change in the primate pancreatic islet cell precursor expressing Sox 17 with the factor.
2 . The method of claim, one wherein the pancreatic islet cell precursors expressing Sox 17 are human cells.
3 . The method of claim one, wherein the primate pancreatic islet cell precursor expressing Sox 17 are the in vitro progeny of a primate pluripotent stem cell.
4 . The method of claim one, wherein the factor is a drug.
5 . The method of claim one, wherein the factor is a solvent.
6 . The method of claim one, wherein the factor is a peptide.
7 . The method of claim one, wherein the factor is a polynucleotide.
8 . The method of claim one, wherein the primate pancreatic islet cell precursor expressing Sox 17 also expresses HNF3β.
9 . The method of claim 1 , wherein observing a change in the primate pancreatic islet cell precursor expressing Sox 17 comprises observing a morphological change in the primate pancreatic islet cell precursor expressing Sox 17.
10 . The method of claim 1 , wherein observing a change in the primate pancreatic islet cell precursor expressing Sox 17 comprises observing a phenotypic change in the primate pancreatic islet cell precursor expressing Sox 17.
11 . A method of screening a factor chosen from a drug, a solvent, a peptide and a polynucleotide for its effect on a primate pancreatic islet cell or islet cell precursor expressing insulin, comprising
a) contacting a cell culture of primate pancreatic islet cells or islet cell precursors expressing insulin with a factor;
b) observing a change in the primate pancreatic islet cell or islet cell precursor expressing insulin after a); and
c) correlating the change in the primate pancreatic islet cell or islet cell precursor expressing insulin with the factor;
wherein the pancreatic islet cell or islet cell precursor is the in vitro progeny of a primate pluripotent stem cell.
12 . The method of claim 11 , wherein the primate pancreatic islet cell or islet cell precursors are human cells.
13 . The method of claim 11 comprising determining if the factor's affects insulin expression or insulin secretion.
14 . The method of claim 11 comprising determining if the compound affects growth of primate pancreatic islet cells or pancreatic islet cell precursors.
15 . The method of claim 11 , wherein the factor is a drug.
16 . The method of claim 11 , wherein the factor is a solvent.
17 . The method of claim 11 , wherein the factor is a peptide.
18 . The method of claim 11 , wherein the factor is a polynucleotide.