Human embryonic stem cells can be coaxed into three-dimensional
structures of retinal cells.
Scientists have
created a three-dimensional, retina-like structure out of human embryonic stem
cells that they hope could someday serve as a retinal transplant for people
with macular degeneration and other diseases of the retina. Their method,
published recently in Journal of Neuroscience Methods, offers a potential new
source of cells for retinal transplants.
In this study, the
researchers first created two types of cells from the human embryonic stem
cells: early-stage retinal cells, and retinal pigment epithelium (RPE) cells,
which provide nourishment to the cells responsible for vision in the retina.
The researchers then grew these two types of cells together in a chamber
designed to expose them to a gradient of concentrations of solutes and
growth-promoting chemicals. The cells could form three-dimensional structures,
a feat rarely achieved with stem cells.
Keirstead believes
that the study points to two important strategies for creating retinal
transplants: growing early retinal cells along with RPE cells, and bathing the
cells in a gradually changing solution that encourages the development of
three-dimensional layers of cells. His team found that this approach generated
early-stage retinal cells that were on the path of differentiating into all of
the various cell types in the retina.
Keirstead believes
that a retinal transplant will work best when made of cells that have not fully
developed. "The three-dimensional layer is purposefully young," he
says. Previous studies have found that younger cells are more likely to
integrate with existing tissue after transplantation, rather than die.
Robert Lanza, chief
scientific officer at Advanced Cell Technologies, who was not involved in the
study, says that his team discovered several years ago that, when turning human
embryonic stem cells into RPE cells, other stem cells would spontaneously form
layers, including patches of photoreceptors. "This paper shows that you
can take advantage of this natural process, and for the first time use tissue
engineering techniques to generate three-dimensional retina-like
structures," he says.
But Lanza is skeptical
about the clinical usefulness of such structures. "You can't just
transplant a retina and restore sight," he says, because it requires
making a series of complex connections with the brain. Although he says there
could prove to be some advantage to using three constructs of cells, "for
the moment, replacing individual cell types might be the best approach for
helping patients suffering from eye disease."
Scientists have been
working on several approaches to retinal transplants. One approach, led by
Advanced Cell Technologies, is to turn human embryonic stem cells into RPE
cells and transplant them into the retina. The therapy would work best in the
early stages of degeneration to halt further progress, rather than to restore
vision that is already lost. Another approach is to transplant stem cells that
are in the early stages of becoming light-sensitive photoreceptors, which has
demonstrated efficacy in mice.