Educating Cells to Produce Insulin
Background
How can scientists program immature stem cells to grow up to be insulin-producing islet cells? Here at the DRI, researchers believe stem cells can be “educated” to make all the right decisions, in the right sequence, until they develop into islet cells.
Research Focus:
This education can be accomplished by delivering to stem cells the same "signals" that guide the development of the pancreas during normal embryonic development. Our 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. When those signals are delivered, they sequentially orchestrate the development of islet cells.
This differentiation, or transformation of one cell type into another, is depicted at a high level in the illustration at right. It shows how our researchers flip molecular protein "switches" that help move an embryonic stem cell down the path to an insulin-producing beta cell. Along the way, the switches activate a series of genes necessary to develop insulin-producing cells, such as:- 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.
The process of stem cell transformation is made possible, in part, by a DRI innovation called the "oxygen sandwich." Developing stem cells require a great deal of oxygen to grow, yet they can suffocate when being cultured in a lab’s petri dish because the plastic container doesn’t allow the cells to get enough oxygen. As an alternative, DRI scientists developed a device that sandwiches developing stem cells between two oxygen sources; a top one that diffuses air through the culture medium, and a bottom one that diffuses air through a silicon membrane incorporating an oxygen binding substance.
Leading to a Cure: How this Research Supports our Mission
Our technique to coax stem cells into insulin-producing islets is described in a paper published in the March 2005 issue of the Journal Diabetes and could ultimately contribute to a cure for the disease by creating a limitless supply of the insulin-producing islet cells destroyed by type 1 diabetes.