A new study published on 13 February in Nature suggests human cells could be reprogrammed to replace the insulin-producing cells destroyed by diabetes, offering a potential new treatment for the degenerative disease (1).
Insulin is a critical hormone required by the human body to regulate blood glucose levels. Specific cells in the pancreas called β-cells are normally responsible for making insulin. However, in type 1 diabetes, the immune system destroys insulin-producing β-cells of the pancreas; whereas with type 2, β-cells either do not produce enough insulin or the body is resistant to the essential hormone. Over time, sugar can build up in the bloodstream, leading to nerve damage and heart disease, among other complications.
Non-β pancreatic cells were previously shown to become β-like and to start producing insulin in mice in the absence of β-cells. Previous studies have also shown that both liver and pancreas cells can be transformed into insulin-producing cells. In particular, α-cells which are found alongside β-cells within the pancreatic islets, regions of the pancreas containing clumps of hormone-secreting cells.
Based on this idea, Prof Pedro Herrera and his team from the University of Geneva have now shown that human pancreatic α-cells can be reprogrammed to produce insulin in response to glucose. More specifically, cells were reprogrammed by introducing DNA encoding for two key transcription factors, pancreatic and duodenal homeobox 1 (Pdx1) ― also known as promotor factor 1 ― and MafA. This enabled the non-β pancreatic cells to start producing insulin ― after one week in culture, almost 40 per cent of human α-cells started producing insulin.
Next, to test whether the insulin-producing α-cells could relieve the clinical signs of type 1 diabetes, the scientists transplanted human cells from different donors into mice lacking insulin-secreting β-cells. The newly transplanted cells were shown to normalise glucose tolerance, secretion, and blood levels. The cells continued to secrete insulin for up to six months in the mice but when the cells transplants were removed, the mice’s blood sugar levels went back up. The same results were obtained using cells from both diabetic and non-diabetic donors, suggesting that the so-called “plasticity” of these cells is not damaged by the disease.
The new findings represent an important step towards new treatments for diabetes, and perhaps, other diseases. Other groups are attempting to produce β-cells from stem cells but this approach could still be hindered by the immune system, whereas, α-cells do not seem to be susceptible to attack. Therefore, the approach of Herrera and colleagues may be more feasible than stem cell strategies. Interestingly, the α-cells can be coaxed to produce insulin without actually becoming β-cells.
While the idea of reprogramming cells to treat disease is an exciting prospect, there are still a number of regulatory and clinical hurdles that will need to be overcome before these treatments can be used in humans.
(1) Furuyama, K. et al. Diabetes relief in mice by glucose-sensing insulin-secreting human α-cells. Nature (2019). DOI: 10.1038/s41586-019-0942-8
(2) Thorel, F. et al. Conversion of adult pancreatic alpha-cells to beta-cells after extreme beta-cell loss. Nature (2010). DOI: 10.1038/nature08894