>> have discovered that insulin-producing beta cells in the pancreas that are attacked in type 1 diabetes are replenished through duplication of existing cells rather than through differentiation of adult stem cells.
Although the experiments, which were done using mice, do not rule out the possibility that there are adult stem cells in the pancreas, the researchers say that they do suggest strongly that embryonic stem cells or mature beta cells may be the only way to generate beta cells for use in cell replacement therapies to treat diabetes.
The research team, which was led by Douglas A. Melton, Thomas Dudley Cabot Professor of the Natural Sciences in the Faculty of Arts and Sciences (FAS) and an HHMI investigator, reports its findings in a research article published in the May 6 issue of the journal Nature. Melton's co-authors include Yuval Dor, Juliana Brown, and Olga I. Martinez, all of Harvard's Department of Molecular and Cellular Biology.
In cell culture, embryonic stem (ES) cells retain the properties of undifferentiated embryonic cells. ES cells have the capacity to make all cell types found in an adult organism. One of the most hotly debated questions in biology is whether adult stem cells, which have been isolated from blood, skin, brain, and other organs, have the same developmental capacity as ES cells.
Researchers have known for some time that ES cells can give rise to pancreatic beta cells during development. "But the more interesting question for us has been what happens in mature pancreatic tissue to both maintain the pancreas and to regenerate it," said Melton. "Previous studies have suggested that there are sources of adult stem cells that might give rise to beta cells. However, those studies had largely depended on histological 'snapshots' of tissues." Those snapshots can only suggest the "geographic" origin of new beta cells and not the identity of the cells from which they arise, Melton noted.
Melton and his colleagues knew that they could finally put such questions to rest if they could tag beta cells in such a way that they could determine unequivocally whether the new cells were made from existing beta cells or from a different reservoir of stem cells. For these studies, they devised a "genetic lineage tracing" technique that involved engineering a mouse whose beta cells contained a telltale genetic marker that could be switched on by administering the drug tamoxifen.
The logic behind the technique is relatively straightforward: When the researchers administer tamoxifen to the adult mice, they can easily follow the marker to determine whether it is inherited by subsequent generations of beta cells. If it is inherited, then the cells expressing the marker are the offspring of pre-existing beta cells.