Photoreceptors created
from induced pluripotent stem cells.
Think twice the next
time you wipe a few flecks of dandruff from your shoulder. You might be
shedding cells that may someday restore human vision.
Thomas Reh and
colleagues at the University of Washington, in Seattle, have generated
light-sensing retinal cells, called photoreceptors, from adult human skin
cells. They then transplanted the cells into a mouse retina, showing that the
photoreceptors integrated normally into the surrounding tissue. This
technological feat raises hopes for the development of treatments for retinal
diseases, such as retinitis pigmentosa and macular degeneration, which cause
visual impairment or blindness in millions of people in the U.S.
Researchers used
induced pluripotent stem (iPS) cell technology, activating a handful of genes
in skin cells in order to revert them to a flexible embryonic state. They then
used previously developed methods to differentiate the cells into
photoreceptors. While Reh's team has done similar experiments using embryonic
stem cells, iPS cells are a preferable source for cell replacement therapies
because they can be derived from the patient. Skin cells are a ready source of
cells that are tissue-matched to the recipient, bypassing problems associated
with immune rejection of stem-cell transplants.
The cells also provide
a new way to study retinal degeneration diseases and to identify drug targets.
Retinitis pigmentosa, for example, is an inherited disorder in which the
photoreceptors begin to die. Retinal cells derived from a patient with the
disease harbor all the genetic mutations that contributed to the patient's
disease, so scientists can try to determine the molecular mechanisms that lead
to cell death. They can then use the cells to screen for molecules that can
slow or stop the damage.
"There are no
good drugs to slow photoreceptor degeneration," said Reh, a neurobiologist
at the University of Washington. "One reason we don't have more molecules
we can test is that we don't have good animal models for many human retinal
diseases."
Scientists will still
need to overcome some serious hurdles before using the cells for
transplantation therapies. The genetic flaws that led to the disease would need
to be fixed before implanting the cells into the eye. And researchers need to
figure out how to get large volumes of cells to integrate effectively into the
retina. In the current experiments, published last month in the journal PLoS
ONE, the number of cells that took root in the mouse eye was too low to restore
visual sensitivity. "We need about 10,000 cells to integrate into the
retina for them to restore function," Reh said.
Future research will
have to explore how well the transplanted photoreceptors connect with other
cell types in the retina and function as an integrated circuit. "The work
still ahead is huge," said Robert Lanza, chief scientific officer at
Advanced Cell Technology. "But this is a very important first
step."