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How can scientists direct the differentiation of stem cells toward islet cell types, and not heart, neurons, liver or skin?
Researchers believe that such "education" may be accomplished by introducing certain signals that guide the formation of the pancreas during normal embryonic development.
Scientists’ understanding of pancreatic development has benefited from an enormous amount of basic research conducted over the last decade. In fact, very few organs have been so well characterized, in terms of their development, as the pancreas.
DRI researchers have been able to identify "master" pancreas genes. When these are activated, they sequentially orchestrate the development of this organ, from the endodermal progenitor cells of the gut to the functional endocrine cells that comprise the islet.
This pathway of progressive differentiation has been laid out in striking detail. Although further work is necessary to understand the fine interactions between these genes, a few of them have been identified as having leading roles in the process:
- Pdx1 - the gene that first sets off the pancreatic program
- Neurogenin 3 - the gene whose expression turns pancreatic stem cells into endocrine cells
- Pax4, Isl-1 and Nkx6.1 - genes involved in beta cell specification.
Using state-of-the-art technologies, investigators in the DRI’s Pancreatic Development & Stem Cell laboratory are trying to recapitulate the development of the pancreas from ES cells.
The idea is to educate these cells to make all the right decisions, in the right sequence, until they develop into islet cells.
Scientists are able to insert these critical signals using protein therapy, a rapidly evolving technology that has been recently developed to deliver proteins and peptides into cells and tissues.
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Embryoid bodies obtained from Embryonic Stem (ES) cells, pictured above, are surprisingly similar to cultured islets. Only a small percentage of these cells, however, express insulin. DRI researchers are harnessing the differentiation potential of ES cells to specifically direct them along the pancreatic lineage.
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