However, the pseudo-stem cells created from mice skin cells, known as induced
pluripotent stem (IPS) stem cells, were not genetically identical like
fetal stem cells, and required different methods of triggering for every
tissue. Now scientists with Rudolph Jaenisch's lab at the Whitehead
Institute for Biomedical Research have discovered a way to transform
any type of tissue into a stem cell and ensure all the produced stem cells
are genetically identical.
The transformation is triggered by the simple release of a drug; no additional
genetic manipulation is necessary. Marius Wernig, one of the paper's two
lead authors and a postdoctoral researcher at the lab stated, "This
technical advancement will allow thousands of identical reprogrammed cells to
be used in experiments."
"Using these cells could help define the milestones of how cells are
reprogrammed and screen for drug-like molecules that replace the potentially
cancer-causing viruses used for reprogramming," added Christopher Lengner,
the other lead author and also a postdoctoral researcher at the lab.
Lengner alluded to an important fear with the current method. Past
efforts used viruses to induce the transformation and it was found that the
viruses could trigger cancer. A batch of stem cells could unwittingly
contain cancer cells that could do far greater damage to the diseased person's
body than the ailment they're being treated for.
While the new research still uses viruses, it is different in two important
ways. First the viruses target a specific spot in the genome. Past
efforts inserted genes anywhere in the genome, raising the likelihood of
cancerous mutation. In the new research, lentiviruses artificial viruses,
are used to randomly insert four genes (Oct4, Sox2, c-Myc and Klf4). All
mice cells processed thusly have the same number of viral integrations in the
same location within the genome. This both leads to genetically identical
stems cells and cuts the cancer risk.
The second important way the research is different is that in its specificity,
researchers can now focus on developing replacement molecules to the viruses,
eliminating the cancer threat. The old research only worked on skin
cells, so the focus was on developing different methods that could trigger
various tissues to become IPS cells. The new method can trigger virtually
any cell -- including cells from the intestine, brain, muscle, kidney, adrenal
gland, and bone marrow -- into becoming an IPS cell.
After the cell is transformed, the cell was further modified to wait to switch
on these genes upon a doxycycline trigger. This allowed researchers to
control when they wanted to transform the cells into stem cells, with a simple
chemical. The new method is much more efficient, with yields up from one
in a thousand cells to one in twenty.
Jaenisch, who is also a professor of biology at Massachusetts Institute of
Technology said, "In experiments, the technique will eliminate many of the
reprogramming process's unpredictable variables and simplify enormously the
research on the reprogramming mechanism and the screening for virus
The research can be found
here in the July 1, 2008, online issue of Nature Biotechnology.
Funding for the research was provided by the Human Frontiers Science
Organization Program, the Ellison Medical Foundation, the Ruth L. Kirschstein
National Research Service Award, and the National Institutes of Health.