This summer HSCI Co-Director Douglas Melton, PhD, and post doctoral fellow Qiao Zhou, PhD, have achieved what has long been an ultimate goal of developmental biologists – directly turning one type of fully formed adult cell into another type of adult cell.
Using a technique they call “direct reprogramming,” the team was able to turn mouse exocrine cells, which make up about 95 percent of the pancreas, into rare insulin-producing beta cells. These beta cells, which comprise about one percent of the pancreas, are the cells that are injured or die off in diabetes.
HSCI Executive Committee member George Daley, MD, PhD, said Melton’s findings are of a caliber that “will revolutionize what is already a revolutionary field.”
In addition to its advancement of the field of regenerative medicine, the work also is a major step forward toward eventually developing a new treatment for diabetes. It is important to note, however, that there are numerous scientific hurdles that lay ahead before a treatment can be tested in humans.
Unlike the process involved in creating induced pluripotent stem cells (iPS), which has generated enormous excitement since its introduction two years ago by Japanese researcher Shinya Yamanaka, MD, PhD, the direct reprogramming technique does not require turning adult cells first into stem cells and then inducing them to differentiate into a desired cell type. Rather the team showed that it is possible to reprogram one type of adult cell directly into another. However, direct reprogramming does not in any way eliminate the need for, or value of, work with iPS cells or human embryonic stem (hES) cells. “We need to attack problems from multiple angles,” said Melton, stressing that his lab is using several approaches and will continue to work with iPS and hES cells.
“We’re intrigued by the possibility that this approach, which has worked for pancreatic insulin-producing cells, could be more widely applied to many kind of cells, especially those that are lost in disease or following injury.” -Douglas Melton, Ph.D.
Sir John Gurdon, FRS, the internationally renowned developmental biologist who was the first scientist to successfully clone an adult vertebrate – a frog – said, “What you really want is a missing cell type, one that is not functioning properly to be derived from something else. But you only want that cell type. So I think this is a really important step forward in exercising what people really wanted and showing how well it can work.”
As is the case with all iPS work thus far, Melton’s experiments involved using viruses to integrate the transcription factors into the target cells. Because of the risks that approach would pose to humans, the team is looking for chemicals that might effectively and, most importantly, safely replace the viruses. See page 3 to read more about “Bringing iPS cells closer to the clinic.”
Joan Brugge, PhD, Chair of the Department of Cell Biology at Harvard Medical School, said the new study “provides exciting new insights into yet another aspect of cell plasticity that was not appreciated previously and that offers great potential therapeutically. Direct reprogramming represents a more straight-forward strategy to treat diseases involving loss of function of specific cell populations than approaches requiring an intermediate embryonic stem cell,” she said.
“We’re intrigued by the possibility that this approach, which has worked for pancreatic insulin-producing cells, could be more widely applied to many kind of cells, especially those that are lost in disease or following injury,” Melton said. “And at the same time, we are exploring the possibility of using this general approach in a clinical context to make new beta cells for patients.”