Pancreatic injury does not evoke progenitors of insulin-producing cell
The origin of beta-cells, the insulin-producing cells in the islets of Langerhans in the pancreas, has been controversial, and now new imaging and cell analysis technology shows that a recent study that seemed to have identified the progenitors of these important cells may have been in error, said researchers from Baylor College of Medicine, Texas Children’s Hospital and the University of Pennsylvania School of Medicine in Philadelphia.
"This is a fundamental question for my field," said Dr. Jake A. Kushner, associate professor of pediatrics - diabetes and endocrinology and a McNair Scholar at BCM and Texas Children’s Hospital. "What is the contribution of stem cells to tissues in the body? If there are stem cells in important tissues of brain, heart and pancreas, it would allow us to cure diseases such as neurological disorders, cardiovascular disease and diabetes. However, it has been difficult to show that there are stem cells in those tissues and to determine their contribution to normal growth and maintenance." A report on his work appears in the journal Diabetes.
Beta cells are critical to production of insulin. They are involved in both types 1 and 2 diabetes.
In a report in cell in 2008, (Cell 123: 197-207: January 25, 2008), Belgian researchers reported an experiment in which they believed that pancreatic injury evoked the potential of stems cells in ducts of the pancreas to produce new beta cells.
"They essentially said pancreatic injury is a unique, regenerative stimulus," said Kushner, who is chief of the Diabetes and Endocrinology Center at Texas Children’s Hospital. The scientists believed the stem cells remained dormant until injury produced some kind of stimulus that turned them back on.
On the other hand, Kushner and others in the field had previously demonstrated that beta cells are self-renewing. In other words, they are their own progenitors, renewing themselves and giving rise to new cells in division.
To try to reproduce the Belgian’s work with newer tools, Kushner and his colleagues used quantitative imaging that allowed them to carefully count the beta cells in the pancreas after injury and special techniques that allowed them to determine the cells from which the new beta cells arose.
"To our surprise, we found that pancreatic injury did not result in generation of new beta cells. When you change the architecture of the pancreas, making it scarred and deformed, the density of beta cells is altered, but the number of such cells remains unchanged. We used lineage tracing tools (that determine the source of the cells) and discovered that all the beta cells appeared to arise from other beta cells."
"In this case of pancreatic injury, beta cell self-renewal remains the only way pancreatic beta cells are being regenerated that we can detect," he said.
It is important to spread the information to other investigators to enable them to direct their efforts into more promising directions, he said.
Others who took part in this work include Matthew M. Rankin, Christopher J. Wilbur, Kimberly Rak, Emily J. Shields and Anne Granger, all of the University of Pennsylvania.
Funding for this work came from the National Institutes of Health (1R01DK064101, 1R01AG040110, P30DK079638), the Juvenile Diabetes Research Foundation, the Commonwealth of Pennsylvania (Center for Excellence in Regenerative Medicine grant 4100043362), and the Robert and Janice McNair Foundation.