Making Insulin Out Of Stem Cells

Embryonic stem cells were turned into insulin-making tissue that was able to keep diabetic mice alive in an experiment that experts say is an important step toward a new treatment for diabetes.

Researchers cautioned that the technique was not yet ready for testing in humans, but said it could lead eventually to using embryonic stem cells to make new insulin-producing islets. The islets of Langerhans are groups of cells in the pancreas, including the beta cells that produce insulin.

In a study appearing this week in the Proceedings of the National Academy of Sciences, Stanford University researchers say they cultured mouse embryonic stem cells until they developed into a tissue that made insulin. After they put the tissue into diabetic mice, the animals were sustained by the insulin produced by the tissue graft.

"We've made something that shares several important properties with the beta cells, but we have not made beta cells," said Ingrid C. Rulifson, a first author of the study. "We believe this is the furthest anyone has gone (in making insulin-producing cells from embryonic stem cells). The fact that we were able to achieve rescue survival in these mice hasn't been demonstrated before in this way."

Dr. Robert Goldstein, chief scientific officer for the Juvenile Diabetes Research Foundation International, said the Stanford finding is "a significant advance" in diabetes research using embryonic stem cells, but he said it will have no immediate human application.

"The principle of being able to take embryonic stem cells and reverse diabetes is an extremely important observation," said Goldstein. He said researchers ultimately hope to use embryonic stem cells to make new beta cells that could be transplanted into diabetics and produce normal levels of insulin.

He called the Stanford study "one of the necessary steps toward achieving this goal," but emphasized that the next steps — translating the mouse data into human therapy — could take many years.

"We can't fix people tomorrow," said Goldstein.

Embryonic stem cells are the ancestral cells from which all the tissue in the body develops. Scientists believe that if they can learn how to direct the transformation of embryonic stem cells they will be able to grow fresh cells to replace those that have died or stopped functioning.

Some forms of diabetes are caused by the death or malfunctioning of the beta cells that make insulin, a hormone essential for regulating sugar in the blood. Researchers hope to use human embryonic stem cells to grow new beta cells, which could then be grafted into diabetic patients to normalize the metabolism of sugar.

In the Stanford study, researchers used special chemicals to cause mouse embryonic stem cells to transform into cell masses that resembled pancreatic islets. Test-tube experiments showed that the cells made insulin.

The researchers then used chemicals to kill the beta cells in a group of laboratory mice, turning the mice into diabetics. The scientists then grafted some of the insulin-producing tissue into the animals. The transplanted tissue made insulin, responding to the levels of sugar in the blood stream of the mice, and kept the mice alive.

Control mice, which had diabetes but did not receive the graft, died.

To prove that it was the transplanted tissue that was making the insulin, the researchers removed the grafts after three weeks. The mice soon died from excess sugar in the blood.

"At least for a short period, we extended the life of these animals convincingly and showed that upon removal of the graft the animals suffered severe relapse of the disease," said Seung K. Kim, a Stanford researcher and senior author of the study.

Kim said that the transplanted tissue produced insulin at only 10 percent to 12 percent of the levels in normal mice and did not produce some of the other hormones or factors made by the normal beta cell.

"This is one step in the right direction," said Kim. He added that "we have a long way to go" before human diabetics can be treated with tissue from embryonic stem cells.