The amount of insulin produced wasn't enough to effectively treat diabetes. Still, the work is a first step toward that eventual goal. It also hints that neural stem cells have many potential uses beyond treating brain disease.

Seung Kim, MD, PhD, lead author and assistant professor of developmental biology at the Stanford University School of Medicine, said the work could lead to new ways of transplanting insulin-producing cells into people with diabetes, eventually providing a cure for the disease.

Most Embryonic Stem Cells Are Contaminated

In past work, Kim and members of his lab enticed mouse embryonic stem cells to transform into insulin-producing cells. When transplanted into diabetic mice, these cells effectively made up for the lost insulin-producing cells in the pancreas, called islet cells, and treated the diabetes.

However, embryonic stem cells are difficult to work with in the lab, and most existing human embryonic stem cell lines are contaminated and can't be transplanted into humans.

Kim thought that using human neural stem cells might be one way to sidestep the problems associated with embryonic stem cell use. The study shows that his intuition was correct.

Neural Stem Cells Can Transform

"When you look at islets cells, you realize that they resemble neurons," Kim said. Like neurons, islet cells respond to external signals by changing their electrical properties and releasing packages of proteins. In the case of islets, that protein is insulin.

Some neurons in mice and humans take the first steps toward producing insulin. In fruit flies, the cells that produce insulin and regulate blood sugar are, in fact, neurons. These observations suggested to Kim that neural stem cells might be able to produce insulin.

Until recently, it was thought that stem cells taken from the brain would only be able to transform into brain-related tissues, such as nerves and support cells.

But a group at the Salk Institute in San Diego recently published a report in which neural stem cells transformed into cells that line blood vessels -- a far cry from a neuron. "That work gave us confidence that these cells could become more than neuronal cells," Kim said.

Responded to Sugar by Producing Insulin

Working with the cells in a lab dish, Kim and postdoctoral fellow Yuichi Hori, MD, PhD, now an associate professor at Kobe University in Japan, added a cocktail of chemicals in a sequence that they knew might prod the stem cells to mature into insulin-producing cells.

After some trial and error, they found the right combination and sequence. The end result was a dish full of cells that could produce insulin and release it in response to sugar added to the environment.

These cells don't perfectly mimic human islet cells. Kim's cells made some -- but not all -- proteins normally made by islet cells, and they continued to make some proteins found in neurons. Nonetheless, the fact that they could respond to sugar by producing insulin was exciting.

Kim's next step was to find out if the cells could perform the same feat in a mouse. The group transplanted the cells into a cavity in the kidney where other types of insulin-producing cells have been found to survive.

When the blood sugar went up in these mice, the cells once again released insulin. After four weeks the cells had survived, continued to produce insulin and had not changed into other cell types or formed tumors.

May Lead to Islet Cell Replacement

Kim noted that the amount of insulin produced wasn't enough to effectively treat diabetes. Still, the work is a first step toward that eventual goal. It also hints that neural stem cells have many potential uses beyond treating brain disease.

This work may have additional value because the method used to produce insulin from neural stem cells is completely new. "The more ways we discover to form insulin-producing cells from stem cells, the more likely it is that stem cells can be used for islet replacement," Kim said.

Kim hopes this work, or related work with other sources of stem cells, one day may lead to the ability to replace human islet cells in people with diabetes. Right now, most people with diabetes face a lifetime of insulin injections.

Some patients can receive cell transplants, but the available sources of cells for transplant are far fewer than the total number of people who could benefit.