Researchers create insulin-producing cells from adult pancreatic cells.

A pancreatic islet, or cluster of hormone-producing cells.

Without using adult stem cells or reverting a cell's programming to its earliest stages, HHMI researchers have flipped an adult cell from one type to another. The team converted one form of adult pancreatic cells into insulin-producing beta cells, the kind of cells destroyed in patients with type 1 diabetes.

The scientists, led by HHMI investigator Douglas A. Melton of Harvard University, repurposed the adult cells by using viruses to introduce three regulatory genes into them. These genes gave the cells their new job descriptions. This novel technique doesn't require wiping out the identity of one cell type before generating a new type. It's like, for example, turning a scientist into a lawyer without sending her all the way back to kindergarten.

“I think this approach could be broadly applicable,” says Melton. “It could be applied to the nervous system or to the cardiovascular system.”

About 95 percent of the pancreas is made up of exocrine cells, which secrete digestive enzymes—the pancreatic cells that Melton's team started with. Only a tiny percentage of the pancreas consists of insulin-producing beta cells, which are organized into discrete clusters called islets. Melton says the next step in his research is to create groups of beta cells capable of replacing the missing beta cells in patients with either type 1 or type 2 diabetes.

“This is a step forward toward eventually developing a treatment for diabetes,” he says. “What we'd like to do is get a collection of those cells together, to make a pancreatic islet.”

Functional beta cells not only produce insulin, they also detect how much glucose is in the blood, providing feedback that adjusts the levels of insulin production. The cells produced by Melton's team do this full job, and electron micrographs confirm that they are full-fledged beta cells. The findings were published on August 27, 2008, in an advance online edition of Nature.

Photo: Melton Lab