Scientists reprogram skin cells into insulin-producing pancreas cells

February 6, 2014

A cure for type 1 diabetes has long eluded even the top experts. Not because they do not know what must be done—but because the tools did not exist to do it. But now scientists at the Gladstone Institutes, harnessing the power of regenerative medicine, have developed a technique in animal models that could replenish the very cells destroyed by the disease. The team's findings, published online today in the journal Cell Stem Cell, are an important step towards freeing an entire generation of patients from the life-long injections that characterize this devastating disease.

Type 1 diabetes, which usually manifests during childhood, is caused by the destruction of ß-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. Once a death sentence, the disease can now be managed with regular glucose monitoring and . A more permanent solution, however, would be to replace the missing ß-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 is that it can potentially provide an unlimited source of functional, insulin-producing ß-cells that can then be transplanted into the patient," said Dr. Ding, who is also a professor at the University of California, San Francisco (UCSF), with which Gladstone is affiliated. "But previous attempts to produce large quantities of healthy ß-cells—and to develop a workable delivery system—have not been entirely successful. So we took a somewhat different approach."

One of the major challenges to generating large quantities of ß-cells is that these cells have limited regenerative ability; once they mature it's difficult to make more. So the team decided to go one step backwards in the life cycle of the cell.

The team first collected , 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, we then transformed these endoderm-like cells into cells that mimicked early pancreas-like cells, which we called PPLC's," said Gladstone Postdoctoral Scholar Ke Li, PhD, the paper's lead author. "Our initial goal was to see whether we could coax these PPLC's to mature into cells that, like ß-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 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.

"Importantly, just one week post-transplant, the animals' glucose levels started to decrease gradually approaching normal levels," continued Dr. 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."

But it was 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 ß-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," explained Dr. Ding.

"I am particularly excited about the prospect of translating these findings to the human system," said Matthias Hebrok, PhD, 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 ß- result in diabetes, bringing us notably closer to a much-needed cure."

Explore further: Targeting a cell cycle inhibitor promotes beta cell replication

Related Stories

Targeting a cell cycle inhibitor promotes beta cell replication

January 16, 2014
Researchers replicated human pancreatic beta cells—which produce insulin—in a mouse model in which donor cells were transplanted. The newly replicated cells retained features of mature beta cells and showed a physiological ...

Loss of function of a single gene linked to diabetes in mice

January 4, 2014
Researchers from the University of Illinois at Chicago College of Medicine have found that dysfunction in a single gene in mice causes fasting hyperglycemia, one of the major symptoms of type 2 diabetes. Their findings were ...

Pancreas stem cell discovery may lead to new diabetes treatments

November 14, 2012
(Medical Xpress)—Stem cells in the adult pancreas have been identified that can be turned into insulin producing cells, a finding that means people with type 1 diabetes might one day be able to regenerate their own insulin-producing ...

Scientists show how insulin-producing cells may fail in diabetes, how they might someday be restored

January 14, 2014
Two new studies led by UC San Francisco (UCSF) scientists shed new light on the nature of beta cells, the insulin-producing cells in the pancreas that are compromised in diabetes.

Cell study offers more diabetic patients chance of transplant

August 29, 2013
Diabetic patients could benefit from a breakthrough that enables scientists to take cells from the pancreas and change their function to produce insulin.

Recommended for you

Want to win at sports? Take a cue from these mighty mice

July 20, 2017
As student athletes hit training fields this summer to gain the competitive edge, a new study shows how the experiences of a tiny mouse can put them on the path to winning.

'Smart' robot technology could give stroke rehab a boost

July 19, 2017
Scientists say they have developed a "smart" robotic harness that might make it easier for people to learn to walk again after a stroke or spinal cord injury.

Engineered liver tissue expands after transplant

July 19, 2017
Many diseases, including cirrhosis and hepatitis, can lead to liver failure. More than 17,000 Americans suffering from these diseases are now waiting for liver transplants, but significantly fewer livers are available.

Lunatic Fringe gene plays key role in the renewable brain

July 19, 2017
The discovery that the brain can generate new cells - about 700 new neurons each day - has triggered investigations to uncover how this process is regulated. Researchers at Baylor College of Medicine and Jan and Dan Duncan ...

New animal models for hepatitis C could pave the way for a vaccine

July 19, 2017
They say that an ounce of prevention is worth a pound of cure. In the case of hepatitis C—a disease that affects nearly 71 million people worldwide, causing cirrhosis and liver cancer if left untreated—it might be worth ...

Omega-3 fatty acids fight inflammation via cannabinoids

July 18, 2017
Chemical compounds called cannabinoids are found in marijuana and also are produced naturally in the body from omega-3 fatty acids. A well-known cannabinoid in marijuana, tetrahydrocannabinol, is responsible for some of its ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.