Reactivating Type 1 diabetics’ pancreatic stem cells to produce insulin
Australian scientists have discovered a way to reactivate pancreatic stem cells to express insulin, a potential new avenue for the treatment of Type 1 diabetics.
They did this using a drug that is approved by the US Food and Drug Administration (FDA) but is not currently licened for diabetes treatment. Although the research is in its initial stages, this approach could lead to future therapies in which newborn insulin producing cells (beta-cells) replace the ones destroyed in Type 1 diabetics
Type 1 diabetes is an autoimmune disease in which insulin-producing beta-cells in the pancreas are selectively destroyed.
“Patients rely on daily insulin injections to replace what would have been produced by the pancreas,” explains El-Osta. “Currently, the only other effective therapy requires pancreatic islet transplantation and while this has improved health outcomes for individuals with diabetes, transplantation relies on organ donors, so it has limited widespread use.”
Pancreatic progenitor cells are stem cells that have the ability to differentiate into the various cells of the pancreas, including beta-cells.
Reprogramming these stem cells into functional insulin-producing beta-cells and implanting them back into the pancreas has been proposed before as a potential alternative treatment for Type 1 diabetes, but it has been poorly understood and remains controversial.
To investigate its feasibility, the team harvested pancreatic stem cells from a Type 1 diabetic donor, as well as from two non-diabetic donors, and treated them with GSK126.
GSK126 inhibits the activity of a key enzyme, EZH2 methyltransferase, that usually works to inhibit the expression of core genes that allow progenitor differentiation into beta-cells.
By treating the cells with GSK126, they restored the expression of these genes, and importantly insulin gene expression, in the progenitor cells from both the non-diabetic and the Type 1 diabetic donors.
It’s unknown whether the results will generalise since the experiments involved the pancreatic cells from a single Type 1 diabetic child, and it’s currently unclear whether the restoration of the beta-cell progenitor genes can be restored in long-standing diabetes.
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