Researchers at Gladstone Institutes have developed a technique in animal models that could replenish the very cells destroyed by the disease.
The team's findings, published in the journal Cell Stem Cell, are an important step towards freeing an entire generation of patients from the life-long injections that characterize type 1 diabetes.
Type 1 diabetes, which usually manifests during childhood, is caused by the destruction of beta-cells, a type of cell that normally resides in the pancreas and produces a hormone called insulin. Without insulin, the body's organs have difficulty absorbing sugars, such as glucose, from the blood.
The disease can now be managed with regular glucose monitoring and Insulin injections. A more permanent solution, however, would be to replace the missing beta-cells. But these cells are hard to come by, so researchers have looked towards stem cell technology as a way to make them.
The power of regenerative medicine is that it can potentially provide an unlimited source of functional, insulin-producing beta-cells that can then be transplanted into the patient. But previous attempts to produce large quantities of healthy beta-cells, and to develop a workable delivery system, have not been entirely successful.
One of the major challenges to generating large quantities of beta-cells is that these cells have limited regenerative ability; once they mature it's difficult to make more. So the researchers decided to go one step backwards in the life cycle of the cell.
The team first collected skin cells, called fibroblasts, from laboratory mice. Then, by treating the fibroblasts with a unique cocktail of molecules and reprogramming factors, they transformed the cells into endoderm-like cells. Endoderm cells are a type of cell found in the early embryo, and which eventually mature into the body's major organs, including the pancreas.
Using another chemical cocktail, researchers then transformed these endoderm-like cells into cells that mimicked early pancreas-like cells ( called PPLC's ).
The initial goal was to see whether they could coax these PPLC's to mature into cells that, like beta-cells, respond to the correct chemical signals and, most importantly, secrete Insulin. And the initial experiments, performed in a petri dish, revealed that they did.
The research team then wanted to see whether the same would occur in live animal models. So they transplanted PPLC's into mice modified to have hyperglycemia, a key indicator of diabetes.
One week post-transplant, the animals' glucose levels started to decrease gradually approaching normal levels, and when researchers removed the transplanted cells, they saw an immediate glucose spike, revealing a direct link between the transplantation of the PPLC's and reduced hyperglycemia.
When the team tested the mice eight weeks post-transplant that they saw more dramatic changes: the PPLC's had given rise to fully functional, insulin-secreting beta-cells.
These results not only highlight the power of small molecules in cellular reprogramming, they are proof-of-principle that could one day be used as a personalized therapeutic approach in patients.
Source: Gladstone Institutes, 2014