JDRF Research

Insulin-Secreting Cells Produced From Unused Pancreatic Tissue

In what may be a significant breakthrough, JDRF-funded researchers in San Diego have discovered that non-secreting tissue in the pancreas can be transformed into insulin-producing cells. The finding suggests a new approach to curing diabetes: coaxing primitive cells in the pancreatic tissue to behave like beta cells. As a result, researchers may be able to identify drug targets that stimulate beta cell regeneration, or grow beta cells for transplantation into humans.

“This discovery raises the possibility of identifying new drug targets for therapeutics for beta cell regeneration. But first we must characterize the signals and receptors activating the generation of new beta cells in this protocol,” JDRF Executive Vice President Richard Insel, M.D., said. “It also could provide a boost to islet transplantation by greatly increasing the amount of donor tissue potentially available.”

The research, led by Fred Levine, M.D., Ph.D., at the University of California, San Diego and the Burnham Institute, was reported  in the journal Nature Medicine.

Researchers looking for potential sources of new beta cells have hoped to find adult stem cells in the pancreas, but none has been discovered. They also have been unable to identify another potential beta cell source in the pancreas: progenitor cells, which are primitive, undeveloped forms of beta cells.

But the last few years have shown significant progress in understanding how pancreatic beta cells might be formed. Two years ago, a study by JDRF-funded researchers in the Harvard laboratory of Douglas Melton, Ph.D., suggested that new beta cells in mice are formed only through replication of existing beta cells. But other studies have found evidence that the body’s ability to create new beta cells—which occurs when the cells proliferate after pancreatic injury or an increase in body mass—cannot be explained by beta-cell replication alone. Now, the San Diego study suggests that the non-secreting, or non-endocrine, portion of the pancreas contains progenitor cells that have the capacity to develop into beta cells.

In these latest experiments, the researchers used painstaking purification and cell culture techniques to isolate cells from pancreatic tissue, which they called “non-endocrine pancreatic epithelial cells,” or NEPECS. After labeling the NEPECS with genetic markers that made the cells easier to identify, they mixed them with fetal pancreatic cells, which are known to contain growth factors that spur cell development. This caused the NEPECS to develop into progenitor cells.

The researchers transplanted the progenitor and fetal cell mixture into mice and allowed it to develop for three months. In this environment, the progenitor cells spontaneously specialized into insulin-secreting cells.

Although making insulin-producing cells from non-endocrine cells is not unprecedented, the efficiency at which the researchers prompted the precursor cells to become beta cells is striking, compared with earlier studies. More than 20 percent of the surviving transplanted cells functioned like insulin-producing beta cells.

The next step for the researchers will be to focus on isolating and characterizing the growth factors that transformed the NEPECs into full-fledged beta cells. They also will try to determine whether all the NEPECs, or just a subset, have beta cell potential.