Insulin Production Unaffected by Adult Stem Cells

Medical Research News, May 8, 2007

Researchers assumed that beta cells, which are insulin producing cells in the pancreas, would be produced by the differentiating adult stem cells that were introduced into the tissue.

Instead, the beat cells replenished their own numbers by slowly dividing.

"Ultimately, if diabetes researchers learn how to control insulin production, we can better treat patients who now can't produce insulin--children and adults with type 1 diabetes," said study leader Jake A. Kushner, M.D., a pediatric endocrinologist at The Children's Hospital of Philadelphia. "This research tells us that we need to better understand what regulates the growth of beta cells, rather than searching for adult stem cells that give rise to beta cells."

In the May issue of Developmental Cell, Dr. Kushner's team reported their results which were based on animal studies.

The breakthrough could establish the basis for eventual therapies since it advances the fundamental understanding of insulin biology. An instant impact on diabetic treatment is not likely due to the study.

Life-saving medication or insulin injections are presently a necessity for patients with type 1 diabetes. Medical researchers hope to restore the body’s capability to manufacture its own insulin by focusing on the future techniques which involve regenerative medicine. Transplanting tissues that contain the beta cells that normally secrete insulin would be one solution. The tissues are referred to as the islets of langerhans which are small masses within the pancreas. After a few years in a patient’s body, experiments showed that islet transplants are typically unsuccessful.

Researchers are in search of a means to produce islets in the laboratory since the supplies are inadequate due to the source being cadavers.

The contentious area of diabetes research concerning beta cell regeneration is an additional prospective implication of the research. Small quantities of islets survive the immune systems attack in patients with long term type 1 diabetes. Enduring beta cells inside patients could be encouraged to proliferate and manufacture healthy quantities of insulin given suitable techniques and adequate biological knowledge.

"We expected to find adult stem cells that differentiate into beta cells," said Kushner. "Such adult stem cells are important in renewing skin, intestines and other tissues."

"However," he added, "we found no evidence for adult stem cells that give rise to beta cells or other pancreatic tissue. We found that all beta cells can replicate, and are, in a sense, their own stem cells."

Beta cells, which develop slowly and can restore themselves, experience an extended waiting phase prior to dividing.

This was an unanticipated discovery for researchers. This delay characteristic has never been observed in mammalian development and is being dubbed a replication refractory period.

Throughout numerous rounds of cell divisions, the researchers were able to analyze the fate of individual cells with the use of a new cell labeling technique.

"Although the cell labeling technique had been described previously by other groups, our group was the first to use it over long periods of time," said Kushner.

The researchers were able to see distinct beta cells in the rat pancreas due to colored dyes that were added in their drinking water in timed succession. The sequence of cell divisions could be determined by observing the noticeable single colors. Indicating that they had divided multiple times from specialized cells, blended colors were observed in the quickly dividing cells of the rat’s intestine. It is possible that the specialized cells were produced from the adult stem cells.

"We expect that other developmental biologists can use this cell labeling technique to track the fate of cells in many other tissues, such as brain and muscle," said Kushner, adding that the technique may also be useful in following cells in cancer research.

Diabetes researchers may be a step closer to influencing the process to benefit patients if these findings open up a new avenue of investigation into how insulin-producing cells develop.

"This research also has implications for type 2 diabetes, in which the body fails to produce and respond to insulin," added Kushner.

Among adolescents and children, the incidence of type 2 diabetes has seen a dramatic rise.