Rewriting Life

Crafting Light-Sensing Cells from Human Skin

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.

Photoreceptors from skin: A photoreceptor cell (green) derived from human skin cells incorporates itself into a mouse retina (red).

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.”

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