UCL scientists have carried out the first successful
transplant of light-sensitive photoreceptor cells
extracted from a synthetic retina, grown ‘in a dish’
from embryonic stem cells.
When transplanted into night-blind mice these cells
appeared to develop normally, integrating into the
existing retina and forming the nerve connections
needed to transmit visual information to the brain.
The study, funded by the Medical Research Council (MRC)
and published in Nature Biotechnology, suggests that
embryonic stem cells could in future provide a
potentially unlimited supply of healthy
photoreceptors for retinal cell transplantations to
treat blindness in humans.
The loss of photoreceptors – light sensitive nerve
cells that line the back of the eye – is a leading
cause of sight loss in degenerative eye diseases
such as age-related macular degeneration, retinitis
pigmentosa and diabetes-related blindness.
There are two types of photoreceptor in the eye –
rods and cones. Rod cells are especially important
for seeing in the dark as they are extremely
sensitive to even low levels of light.
Previous work by Professor Robin Ali and his team at
the UCL Institute of Ophthalmology and Moorfields
Eye Hospital has shown that transplanting immature
rod cells from the retinas of healthy mice into
blind mice can restore their sight. However, in
humans this type of therapy would not be practical
for the thousands of patients in need of treatment.
Using a new laboratory technique involving 3D
culture and differentiation of mouse embryonic stem
cells, which was developed recently in Japan, Prof
Ali’s team were able to grow retinas containing all
the different nerve cells needed for sight.
Professor Ali, UCL Institute of Ophthalmology and
Moorfields Eye Hospital, who led the research, said:
“Over recent years scientists have become pretty
good at working with stem cells and coaxing them to
develop into different types of adult cells and
tissues. But until recently the complex structure of
the retina has proved difficult to reproduce in the
lab. This is probably because the type of cell
culture we were using was not able to recreate the
developmental process that would happen in a normal
embryo.
“The new 3D technique more closely mimics normal
development, which means we are able to pick out and
purify the cells at precisely the right stage to
ensure successful transplantation.
The next step will be to refine this technique using
human cells to enable us to start clinical trials.”
The researchers grew retinal precursor cells using
the new 3D culture method and compared them closely
with cells developed normally, looking for different
markers at different stages of development. They
also carried out tests to look at the genes being
expressed by the two types of cells to make sure
they were biologically equivalent.
They then transplanted around 200,000 of the
artificially grown cells by injecting them into the
retina of night blind mice.
Three weeks after transplantation the cells had
moved and integrated into the recipient mouse retina
and were beginning to look like normal mature rod
cells. These cells were still present six weeks
after transplantation.
The researchers also saw nerve connections (synapses),
suggesting that the transplanted cells were able to
connect with the existing retinal circuitry.
Dr Rob Buckle, Head of Regenerative Medicine at the
MRC, said: “Regenerative medicine holds a great deal
of promise for treating degenerative diseases and
the eye is one area in particular where scientists
are making very rapid progress. This study is an
important milestone on the road to developing a
widely available cell therapy for blindness as it
proves unequivocally that embryonic stem cells can
provide a renewable source of photoreceptors that
could be used in treatments.”
For more information
Nature biotecnology
Photoreceptor precursors derived from
three-dimensional embryonic stem cell cultures
integrate and mature within adult degenerate retina
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