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Reprogrammed Human Pancreatic Cells Reprogrammed to Create Insulin

Reporter: Irina Robu, PhD

A  new study proposes that various cells can be modified to take a place of an insulin producing cell to help control sugar levels.  Researchers from University of Lincoln, UK report coaxing human pancreatic cells that don’t normally make insulin (a hormone that regulates the amount of glucose in the blood), to change their identity and begin producing the hormone. When implanted in mice, these reprogrammed cells relieved symptoms of diabetes, raising the opportunity that the method could one day be used as a treatment in people.

It is known that beta cells normally respond by releasing insulin when blood sugar levels rise after eating, which in turn stimulates to start absorbing sugars. In people with diabetes, this system breaks down, leading to high blood sugar levels that can harm the body and cause illness. In type 1 diabetes, the immune system attacks and destroys β-cells; in type 2, the β-cells do not produce enough of the hormone, or the body becomes resistant to insulin.

Scientists have previously revealed in mouse studies that if β-cells are destroyed, alternative type of pancreatic cell, called α-cells become more β-like and start making insulin. These α-cells normally yield the hormone glucagon which are originate together with β-cells in clumps of hormone-secreting cells called pancreatic islets or islets of Langerhans. Preceding studies showed that two proteins that control gene expression seemed to have an important role in coaxing α-cells to produce insulin in mice: Pdx1 and MafA.

At the same time as researchers from University of Lincoln, researchers from Pedro Herrera group at University of Geneva, wondered whether producing more of these proteins in human α-cells would have a similar result. They first took islet cells from human pancreases, and separated out the individual cell types which were then introduced DNA that encoded Pdx1 and MafA proteins into the α-cells, before clumping them back together.

After one week in culture, almost 40% of the human α-cells were producing insulin, while control cells that hadn’t been reprogrammed were not. The reprogrammed cells showed an increase in the expression of other genes related to β-cells, which were then implanted into diabetic mice, which had their β-cells destroyed and found that blood-sugar levels went down to normal levels. When the cell grafts were removed, the mice’s blood sugar shot back up.

Results of the experiment show that if α-cells or other kinds of islet cells could be made to start producing insulin in this way in diabetes patients’ quality of life will improve. According to Herrera before drawing conclusions about the efficacy of their approach, they will need to test the hybrid cells with other antibodies present in type-1 diabetes that could potentially attack those cells. But the research demonstrates that there is a lot of plasticity in the hormonal system of the human pancreas.

SOURCE

https://www.nature.com/articles/d41586-019-00578-z