Scientists Turn Skin Cells into Insulin-Producing Pancreas Cells
A first step toward a cure for type-1 diabetes was taken recently by scientists who developed a technique in animal models that could replenish insulin-producing β-cells, the very same cells destroyed by the disease.
Once considered a death sentence, type-1 diabetes can now be managed with regular glucose monitoring and insulin injections. A more permanent solution, however, would be to replace the missing β-cells, which normally reside in the pancreas and produces a hormone called insulin. Without insulin, a person's body has difficulty absorbing sugars, such as glucose, from the blood. The best way to do that, according to the researchers, is to make them from stem cells.
"The power of regenerative medicine is that it can potentially provide an unlimited source of functional, insulin-producing β-cells that can then be transplanted into the patient," said Dr. Sheng Ding, a co-author of the study in a statement. "But previous attempts to produce large quantities of healthy β-cells and to develop a workable delivery system-have not been entirely successful. So we took a somewhat different approach."
Once a β-cell matures, it's difficult for it to regenerate, so the scientists decided to roll back the clock on the life cycle of the cells.
To do this, Ding collected skin cells from laboratory mice and treated them with a unique 'cocktail' of molecules and reprogramming factors in order to transform the cells into endoderm-like cells, which are found in early embryos.
"Using another chemical cocktail, we then transformed these endoderm-like cells into cells that mimicked early pancreas-like cells, which we called PPLC's," said Ke Li, the paper's lead author. "Our initial goal was to see whether we could coax these PPLC's to mature into cells that, like β-cells, respond to the correct chemical signals and-most importantly-secrete insulin. And our initial experiments, performed in a petri dish, revealed that they did."
The team then tested their results on live animals by transplanting the PPLC's into mice with hyperglycemia, a key indicator of diabetes.
"Importantly, just one week post-transplant, the animals' glucose levels started to decrease, and gradually approached normal levels," continued Li. "And when we removed the transplanted cells, we saw an immediate glucose spike, revealing a direct link between the transplantation of the PPLC's and reduced hyperglycemia."
Eight weeks post-transplant the researchers saw a dramatic change: the PPLC's had given rise to functional, insulin-secreting β-cells.
"These results not only highlight the power of small molecules in cellular reprogramming, and are proof-of-principle that could one day be used as a personalized therapeutic approach in patients," explained Dr. Ding.
"I am particularly excited about the prospect of translating these findings to the human system," said Matthias Hebrok, the Hurlbut-Johnson Distinguished Professor of Diabetes Research, who is one of the study's authors and director of the UCSF Diabetes Center. "Most immediately, this technology in human cells could significantly advance our understanding of how inherent defects in β-cells result in diabetes, bringing us notably closer to a much-needed cure."
The study was published in Cell Stem Cell.