The North West Embryonic Stem Cell Centre

Targeted differentiation to insulin-secreting cells

A number of recent papers have provided a baseline from which to establish effective protocols to differentiate human embryonic stem cells to pancreatic β-cells. Published protocols to date are inefficient, with at best around 12% ‘β-cells’ still poorly responsive to normal stimulants of insulin secretion. NWESCC has embarked on the evaluation of a protocol to induce established pluripotent hES cell lines to committed endoderm precursors using sequential changes of growth factors. The endoderm precursor cell gives many endoderm lineages including β-cells. Our researchers are developing protocols to enrich for endoderm precursors and perfecting selection methods together with the next phase of inducing these cells to form pancreatic β-cells.

We believe a stepwise approach to induction of pancreatic β-cells will be most effective. We can efficiently induce expression for a number of mesendoderm and endoderm markers in our feeder free conditions and are in the process of refining our protocols for induction of markers of developing gut. We are working on the production of physiologically responsive pancreatic cells with high efficiency.

Genetic modification of these cells is being investigated to achieve a more efficient and reproducible differentiation. Although it is unlikely that genetically modified cells would be desirable in a therapeutic context, this modeling will generate invaluable data on endogenous temporal expression and the effects of over-expression during differentiation to allow fine tuning of induction regimens.

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Research technician

A stepwise approach

foxA2/HNF3β immunostaining – (ENDODERM MARKER #1) plated feeder-free hues7 EBs
Researchers for NWESCC are working towards establishing effective protocols for differentiating human embryonic stem cells to pancreatic β-cells.