September 03, 2004
Stem Cells Renew Hope for Fading Hair Follicles
Howard Hughes Medical Institute (HHMI) researchers have isolated
stem cells from the skin of mice and shown that they have the power to
self-renew and differentiate into skin and functioning hair follicles
when grafted onto mice. The findings mean that the human equivalent of
these stem cells — which scientists are also trying to isolate —
could ultimately be used to regenerate skin and hair, the researchers
said.
Stem cells — isolated from embryos or from adult tissue — are
immature progenitor cells with the capability to differentiate into a
variety of specialized cells that form tissues and organs. Scientists
are working toward using stem cells to grow mature specialized cells
that could regenerate damaged or diseased skin, brain, heart or other
organs. The new findings constitute another step toward understanding
how to mimic the chemical signals that the cells require to
differentiate into mature tissues, according to Howard Hughes Medical
Institute investigator Elaine Fuchs. Fuchs and colleagues at The
Rockefeller University published their findings in the September 3,
2004, issue of the journal Cell.
“I think clinicians will be interested in the fact that both of these populations can produce hair follicles after culture.”
Elaine Fuchs
According to Fuchs, previous studies in her laboratory and others
suggested that a structure called the bulge, which is located within
each hair follicle, might contain stem cells. Those studies hinted that
the stem cells might provide the source of both new skin and hair
follicles.
“However, two major questions remained,” said Fuchs.
“One was whether there was a single type of multipotent stem cell
within the bulge, or a bag of different kinds of stem cells — some of
which could repopulate the epidermis and others that could produce hair
follicles.
“The second major question was whether these cells were
capable of undergoing self-renewal. And of particular interest to
clinicians was whether they could undergo division in a lab dish and
still have the capability to perform either epidermal repair or
hair-follicle generation.”
To answer those questions, Fuchs and her colleagues first isolated
stem cells from the bulge by fusing antibodies to characteristic cell
surface molecules.
“An important aspect of this paper was that we found we could
isolate and characterize these cells by taking advantage of the
cell-surface markers that we had previously identified from molecular
profiling experiments,” said Fuchs. “We can now utilize
similar methods to begin to compare mouse and human skin stem
cells.”
The scientists' analyses of the biochemical characteristics of the
isolated mouse stem cells revealed that the bulge contained two
distinct populations of stem cells. One type, called
“basal” cells, is active during early development. In
contrast the “suprabasal” cells appear only after the first
hair generation cycle. This distinction offers biologists an
opportunity to compare the two groups of cells, in terms of the control
that the bulge exerts over their proliferation and differentiation.
Despite the fact that the stem cells expressed many different genes,
both populations were capable of self-renewal when grown in culture,
said Fuchs. The researchers also found that both types of cells — even
after being cultured — produced hair follicles when grafted onto the
skin of a strain of hairless mice.
“I think clinicians will be interested in the fact that both
of these populations can produce hair follicles after culture,”
said Fuchs. “Previously, researchers have done similar transplant
experiments with dissected parts of the hair follicle. And, while
they've had evidence that hair follicle structures were forming, they
didn't see generation of hair.
“In contrast, in our experiments, we saw quite a density of
hairs, in some cases at a density that's very similar to that of normal
mouse fur,” said Fuchs. “While we are not yet able to
achieve such density a hundred percent of the time, the fact that we do
get such density in some cases tells us that the system is working
well. We just need to tweak it to the point where we can get such
results consistently,” she said.
Importantly, said Fuchs, the stem cells they isolated showed a
molecular signature of gene activity that demonstrates their
“stemness.” Such characteristics, she said, represent the
beginning of a broader effort to compare the genes activated in many
stem cell types, to understand the factors that control their
proliferation and differentiation.
“The information that we have now on the 'stemness' genes is
allowing us to narrow in on some of the similarities among stem cells
of the body,” she said. “I believe this profiling
information will ultimately give us some very good clues as to how stem
cells respond to various external cues. And this information will help
us understand how we can coax stem cells down one specific lineage or
another in culture.”
The findings also emphasize the promise that such studies hold for
the treatment of such skin disorders as ulcers or injury, as well as
the generation of hair follicles from stem cells, she said.
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