Identity of Mature Cells Successfully Changed

Nature, August 27, 2008

A team of researchers led by Dr. Douglas Melton of the Harvard Stem Cell Institute, in collaboration with researchers at the Howard Hughes Medical Institute, have successfully transformed mature cells in mice into a different type of cell.

The research, which was published today in the online journal Nature, involves the reprogramming of a cellular "identity switch", which is a type of master control for determining which genes in the cell are activated and which remain inactive. The findings are the first of their kind to be conducted in vivo, with the transformation of ordinary pancreatic cells into the more specialized beta islet cells, which are the cells that produce insulin.

Such research represents a further step in the ongoing effort by many scientists to avoid embryonic stem cells and their ethical dilemmas, by working with pluripotent stem cells from non-embryonic sources. Earlier studies with iPS (induced pluripotent stem) cells, for example, used ordinary skin cells from adults that were reprogrammed into a more primitive state, from which they could then be directed to develop into various types of tissue, at least theoretically. One of the problems encountered with the iPS cells, however, is the difficulty of controlling their differentiation into the desired, specialized tissue. This latest discovery, however, changes a mature cell into another mature cell without having to revert back to a primitive cell as an intermediate stage.

Using mice in which the beta islet cells had been destroyed, Dr. Melton's team injected the pancreas of the mice with a viral "vector" that delivered 3 genes into the ordinary pancreatic cells, which 3 days later were found to have been converted into the insulin-producing beta islet cells. After a week, over 20% of the cells had begun producing insulin. The newly formed cells were identified as beta islet cells both morphologically (in structure) as well as functionally. According to Dr. Richard Insel, executive vice president of research at the Juvenile Diabetes Research Foundation, this research represents "an amazingly efficient effect", much more so than that seen from iPS cells thus far.

Dr. Melton has a personal interest in diabetes, and has been a leading researcher in the field since 1993, when his infant son was diagnosed with Type 1 diabetes. However, scientists are quick to observe that these findings have a wide range of implications which extend far beyond diabetes. Researchers at Stanford, for example, are currently studying applications of the same procedure with liver cells. Indeed, the findings mark an important achievement in understanding the molecular signals that are involved in the reprogramming of cells, which is relevant to the treatment of virtually every type of disease.