Immunofluorescence microscopy image of the induced neural stem cells using antibodies against two neural stem cell markers SSEA1 (red color) and Olig2 (green color). MPI for Molecular Biomedicine |
Scientists
at the Max Planck Institute for Molecular Biomedicine in Münster,
Germany, have succeeded in obtaining somatic stem cells from fully
differentiated somatic cells. Stem cell researcher Hans Schöler and his
team took skin cells from mice and, using a unique combination of growth
factors while ensuring appropriate culturing conditions, have managed
to induce the cells’ differentiation into neuronal somatic stem cells.
“Our
research shows that reprogramming somatic cells does not require
passing through a pluripotent stage,” explains Schöler. “Thanks to this
new approach, tissue regeneration is becoming a more streamlined—and
safer—process.”
Up
until now, pluripotent stem cells were considered the ‘be-all and
end-all’ of stem cell science. Historically, researchers have obtained
these ‘jack-of-all-trades’ cells from fully differentiated somatic
cells. Given the proper environmental cues, pluripotent stem cells are
capable of differentiating into every type of cell in the body, but
their pluripotency also holds certain disadvantages, which preclude
their widespread application in medicine.
According
to Schöler, “pluripotent stem cells exhibit such a high degree of
plasticity that under the wrong circumstances they may form tumours
instead of regenerating a tissue or an organ.”
Schöler’s
somatic stem cells offer a way out of this dilemma: they are ‘only’
multipotent, which means that they cannot give rise to all cell types
but merely to a select subset of them—in this case, a type of cell found
in neural tissue—a property, which affords them an edge in terms of
their therapeutic potential.
To
allow them to interconvert somatic cells into somatic stem cells, the
Max Planck researchers combined a number of different growth factors,
proteins that guide cellular growth.
“One
factor in particular, called Brn4, which had never been used before in
this type of research, turned out to be a genuine ‘captain’ who very
quickly and efficiently took command of his ship—the skin cell—guiding
it in the right direction so that it could be converted into a neuronal
somatic stem cell,” explains Schöler.
This
interconversion turns out to be even more effective if the cells,
stimulated by growth factors and exposed to just the right environmental
conditions, divide more frequently.
“Gradually,
the cells lose their molecular memory that they were once skin cells,”
explains Schöler. It seems that even after only a few cycles of cell
division the newly produced neuronal somatic stem cells are practically
indistinguishable from stem cells normally found in the tissue.
Schöler’s
findings suggest that these cells hold great long-term medical
potential: “The fact that these cells are multipotent dramatically
reduces the risk of neoplasm formation, which means that in the
not-too-distant future they could be used to regenerate tissues damaged
or destroyed by disease or old age; until we get to that point,
substantial research efforts will have to be made.” So far, insights are
based on experiments using murine skin cells; the next steps now are to
perform the same experiments using actual human cells. In addition, it
is imperative that the stem cells’ long-term behaviour is thoroughly
characterized to determine whether they retain their stability over long
periods of time.
“Our
discoveries are a testament to the unparalleled degree of rigor of
research conducted here at the Münster Institute,” says Schöler. “We
should realize that this is our chance to be instrumental in helping
shape the future of medicine.”
At
this point, the project is still in its initial, basic science stage
although “through systematic, continued development in close
collaboration with the pharmaceutical industry, the transition from the
basic to the applied sciences could be hugely successful, for this as
well as for other, related, future projects,” emphasizes Schöler. This,
then, is the reason why a suitable infrastructure framework must be
created now rather than later.
“The
blueprints for this framework are all prepped and ready to go—all we
need now are for the right political measures to be ratified to pave the
way towards medical applicability.”
