Scientists experimenting with stem cell approaches to alternative organ cell development have discovered a potential breakthrough in the way type 1 diabetes is treated, a new study reports.
In the sibling rivalry between type 1 and type 2 diabetes, in sheer popularity alone, type 2 would be the decisively cooler older sibling. Roughly 90 percent of all diabetes cases are type 2, characterized by a deficiency in the pancreas to produce the hormone insulin, which regulates blood glucose levels. But type 1’s remaining market share of 10 percent is actually far more lethal than type 2, as type 1 diabetics don’t simply have an insulin deficiency, which can be controlled through diet and exercise, but a total lack of insulin production.
Both forms demand the regulation of blood glucose levels, but the consequences of ignoring that demand are far more severe in type 1 patients. For years, this has motivated researchers to develop effective treatment options that jumpstart the production of insulin. They’ve known, for instance, that halted production of insulin was a result of destroyed ß-cells, which also live in the pancreas and typically disappear during childhood. (Type 1 diabetes is often referred to as juvenile diabetes.) While diabetics can stay healthy with regular insulin injections, the ideal solution would be to replace the missing ß-cells — something scientists don’t yet have the tools to do, but, with the current study, is on the horizon.
"The power of regenerative medicine is that it can potentially provide an unlimited source of functional, insulin-producing ß-cells that can then be transplanted into the patient," said Gladstone Institute researcher and professor at the University of California San Francisco, Dr. Sheng Ding, in a statement. One the obstacles, however, is that mature ß-cells aren’t easily replicated. So the team approached the cell from one stage earlier.
Using mouse models to conduct their study, the team extracted batches of skin cells, known as fibroblasts. Then, by treating the fibroblasts with a specific blend of molecules and reprogramming agents, they transformed the fibroblasts into cells found in the early embryo, known as endoderm cells. These cells eventually mature into the body’s organs, including the pancreas. A third transformation yielded pancreas-like cells, which the team called PPLCs.
"Our initial goal was to see whether we could coax these PPLCs to mature into cells that, like ß-cells, respond to the correct chemical signals and — most importantly — secrete insulin,” explained Gladstone researcher Dr. Ke Li. “And our initial experiments, performed in a petri dish, revealed that they did.” Subsequent live animal models showed the same success for mice with induced hyperglycemia (high blood sugar). And when the team removed the cells, glucose levels immediately spiked, “revealing a direct link between the transplantation of the PPLC's and reduced hyperglycemia."
But perhaps the hallmark of the study was the eight-week check-in. Researchers found that mice in the experimental group had begun producing insulin-secreting ß-cells independently. Such results offer hope to scientists who one day seek to test the technique on human models. In the meantime, the team plans on further investigating the link between a lack of ß-cells and the eventual tip toward full-blown diabetes.
"These results not only highlight the power of small molecules in cellular reprogramming,” Ding said. “They are proof-of-principle that could one day be used as a personalized therapeutic approach in patients.”
Source: Li K, Zhu S, Russ H, et al. Small Molecules Facilitate the Reprogramming of Mouse Fibroblasts into Pancreatic Lineages. Cell Stem Cell. 2014.