Imma Perfetto
Cosmos science journalist
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.
The results have been reported in new study published in the journal Signal Transduction and Targeted Therapy.
“We consider the research novel and an important step forward towards developing new therapies,” says senior author Professor Assam El-Osta, an epigeneticist and leader of the El-Osta research group in the Department of Diabetes, Central Clinical School, at Monash University, Australia.
Reprogramming pancreatic stem cells
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.
Implications for future research
But the authors acknowledge some important limitations of the study.
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.
“As we face a globally ageing population and the challenges of escalating numbers of Type 2 diabetes, which is strongly correlated with increases in obesity, the need for a cure for diabetes is becoming more urgent,” adds co-author Dr Keith Al-Hasani, a researcher in the El-Osta research group.
“Before you get to patients, there are many issues to be resolved. More work is required to define the properties of these cells and establish protocols to isolate and expand them.
“I would think therapy is pretty far away, however, this represents an important step along the way to devising a lasting treatment that might be applicable for all types of diabetes.”