Researchers have succeed in producing photoreceptors from human embryonic stem cells
Newswise, October 6, 2015--Age-related
macular degeneration (AMRD) could be treated by transplanting photoreceptors
produced by the directed differentiation of stem cells, thanks to findings
published today by Professor Gilbert Bernier of the University of Montreal and
its affiliated Maisonneuve-Rosemont Hospital.
ARMD is a common eye problem caused by
the loss of cones. Bernier’s team has developed a highly effective in vitro
technique for producing light sensitive retina cells from human embryonic stem
cells.
“Our method has the capacity to
differentiate 80% of the stem cells into pure cones,” Professor Gilbert
explained. “Within 45 days, the cones that we allowed to grow towards
confluence spontaneously formed organised retinal tissue that was 150 microns
thick. This has never been achieved before.”
In order to verify the technique,
Bernier injected clusters of retinal cells into the eyes of healthy mice. The
transplanted photoreceptors migrated naturally within the retina of their host.
“Cone transplant represents a
therapeutic solution for retinal pathologies caused by the degeneration of
photoreceptor cells,” Bernier explained.
“To date, it has been difficult to
obtain great quantities of human cones.” His discovery offers a way to overcome
this problem, offering hope that treatments may be developed for currently
non-curable degenerative diseases, like Stargardt disease and ARMD.
“Researchers have been trying to achieve
this kind of trial for years,” he said. “Thanks to our simple and effective
approach, any laboratory in the world will now be able to create masses of
photoreceptors.
“Even if there’s a long way to go before
launching clinical trials, this means, in theory, that will be eventually be
able to treat countless patients.”
The findings are particularly
significant in the light of improving life expectancies and the associated
increase in cases of ARMD. ARMD is in fact the greatest cause of blindness
amongst people over the age of 50 and affects millions of people worldwide.
And as we age, it is more and more
difficult to avoid – amongst people over 80, this accelerated aging of the
retina affects nearly one in four. People with ARMD gradually lose their
perception of colours and details to the point that they can no longer read,
write, watch television or even recognize a face.
ARMD is due to the degeneration of the
macula, which is the central part of the retina that enables the majority of
eyesight.
This degeneration is caused by the
destruction of the cones and cells in the retinal pigment epithelium (RPE), a
tissue that is responsible for the reparation of the visual cells in the retina
and for the elimination of cells that are too worn out.
However, there is only so much
reparation that can be done as we are born with a fixed number of cones. They
therefore cannot naturally be replaced. Moreover, as we age, the RPE’s
maintenance is less and less effective – waste accumulates, forming deposits.
“Differentiating RPE cells is quite
easy. But in order to undertake a complete therapy, we need neuronal tissue
that links all RPE cells to the cones. That is much more complex to develop,”
Bernier explains, noting nonetheless that he believes his research team is up
to the challenge.
Bernier has been interested in the genes
that code and enable the induction of the retina during embryonic development
since completing his PhD in Molecular Biology in 1997.
“During my post-doc at the Max-Planck
Institute in Germany, I developed the idea that there was a natural molecule
that must exist and be capable of forcing embryonic stem cells into becoming
cones,” he said.
Indeed, bioinformatic analysis led him
to predict the existence of a mysterious protein: COCO, a “recombinational”
human molecule that is normally expressed within photoreceptors during their
development.
In 2001, he launched his laboratory at
Maisonneuve-Rosemont Hospital and immediately isolated the molecule.
But it took several years of research to
demystify the molecular pathways involved in the photoreceptors development
mechanism. His latest research shows that in order to create cones, COCO can
systematically block all the signalling pathways leading to the differentiation
of the other retinal cells in the eye.
It’s by uncovering this molecular
process that Bernier was able to produce photoreceptors. More specifically, he
has produced S-cones, which are photoreceptor prototypes that are found in the
most primitive organisms.
Beyond the clinical applications,
Professor Bernier’s findings could enable the modelling of human retinal
degenerative diseases through the use of induced pluripotent stem cells,
offering the possibility of directly testing potential avenues for therapy on
the patient’s own tissues.
About this study:
Shufeng Zhou, Anthony Flamier, Mohamed
Abdouh, Nicolas Tétreault, Andrea Barabino, Shashi Wadhwa and Gilbert Bernier
published “Differentiation of human embryonic stem cells into cone
photoreceptors through simultaneous inhibition of BMP, TGFβ and Wnt signaling”
in Development on October 6, 2015. DOI: 10.1242/dev.125385
Gilbert Bernier is director of the Stem
Cell and Developmental Biology Laboratory at Maisonneuve-Rosemont Hospital and
a professor with the Department of Neuroscience and the Department of
Opthalmology at the University of Montreal.
This work was supported by grants from
the Foundation Fighting Blindness Canada, Turmel Family Foundation for Macular
Degeneration Research, Canadian Stem Cell Network, C. Durand Foundation, the GO
Foundation, and Natural Science and Engineering Research Council of Canada
[grant #250970-2012].
Professor Bernier was supported by the
Fonds de recherche du Québec – Santé.
The University of Montreal is officially
known as Université de Montréal. Maisonneuve Rosemont Hospital is part of
Centre intégré universitaire de santé et de services sociaux de
l'Est-de-l'Île-de-Montréal.
