Destruction of insulin-producing beta cells in the pancreas is at the heart of type 1 and type 2 diabetes. (Agencies)
"We are looking for ways to make new beta cells for these patients to one day replace daily insulin injections," said Ben Stanger, an assistant professor at University of Pennsylvania.
Transplanting islet cells to restore normal blood sugar levels in patients with severe type 1 diabetes is one approach to treating the disease. Using stem cells to create beta cells is another area of investigation.
However, both of these strategies have limitations."Our results demonstrate that the intestine could be an accessible and abundant source of functional insulin-producing cells," Stanger noted.
In the new research, Stanger and his team introduced the three beta-cell reprogramming factors Pdx1 (P), MafA (M) and Ngn3 (N) - collectively called PMN - into the acinar cells of the pancreas. Remarkably, this manipulation caused the cells to take on some structural and physiological features of beta cells.
They expressed PMN in a wide spectrum of tissues in one-to-two-month-old mice. Three days later the mice died of hypoglycemia.
The team knew they were on to something given that some of the mouse cells - cells other than acinar cells - were making way too much extra insulin.
"In tracking down which cell type it was, we saw transient expression of the three factors in crypt cells of the intestine near the pancreas," Stanger explained.
They dubbed these beta-like, transformed cells 'neoislet' cells. These cells express insulin and show outward structural features akin to beta cells.
The neoislets are also responsive to glucose - when exposed to glucose they release insulin. The cells were also able to improve hyperglycemia in diabetic mice. What is more, expressing PMN in human intestinal 'organoids' - miniature intestinal units that can be grown in culture - also converted intestinal epithelial cells into beta-like cells.
"Our ultimate goal is to obtain epithelial cells from diabetes patients who have had endoscopies, expand these cells, add PMN to them to make beta-like cells, and then give them back to the patient as an alternate therapy," Stanger expressed.The report was published in the journal Cell Reports.
Destruction of insulin-producing beta cells in the pancreas is at the heart of type 1 and type 2 diabetes.