CELL THERAPY AND CELL TRANSPLANTATION
have we achieved?
Transplantation of retinal precursor cells
We have recently examined the ability of transplanted cells to connect
to the retina in an adult eye. Instead of using stem cells we performed
these experiments with retinal progenitors, cells from the eye of
a newly born mouse that are about to turn into photoreceptors. When
these cells were injected into the eye of another young mouse, a
small percentage would integrate properly into the retina. This
was a promising result, but not very surprising as the retina of
the recipient mouse was being formed at the time. Therefore it was
receptive to connecting up new cells. The next step was to inject
these same progenitor cells into an adult eye, which was already
fully formed. Again the cells appeared to integrate and connect
properly into the retina. As our immature photoreceptors could integrate
into an adult retina, we finally attempted to show that transplanted
cells could improve the function of the retina. The retinal progenitor
cells were injected into the retinas of adult mice with retinitis
pigmentosa. As is the case in the adult normal mice a fraction of
the transplanted retinal cells integrated into the retina. Before
treatment the retinas of these mice are not sensitive to light,
but we could show that after integration of the healthy progenitor
cells, a flash of light resulted in a measurable electric response
in the nerve that runs from the eye to the brain. We could also
show that the pupil reflex, the closing of the pupil after shining
light into the eye, was restored after the transplantation. These
experiments for the first time provided proof that transplanted
cells had wired up correctly and were signalling when they were
stimulated with light.
These results are very encouraging, as they predict that if the
right cells can be found, it is probable that some vision can be
restored in patients. We are continuing these experiments to find
methods that improve the integration process, thereby allowing higher
numbers of healthy cells to connect to the retina.
Isolation and culture of stem cells
are a number of requirements for a perfect stem cell source. Ideally
we would like to be able to grow up stem cells from the patients’
own tissue, as that would solve problems such as rejection of the
transplant. Secondly, the cells need to grow well in the laboratory,
so that from a small number of cells we can grow up sufficient numbers
to treat a substantial proportion of the retina. Finally, the cells
need to be able to turn into photoreceptor cells when they are injected,
a process called differentiation.
We are currently
designing the methods to culture stem cells from several sources,
such as the iris and the edge of the retina. At the moment these
experiments use mainly tissue from various animals, but when the
procedure will be performed on patients, a small biopsy might be
taken from the patient’s eye for use as a source of cells.
To grow up the animal stem cells, the correct culture conditions
must be found that allow the cells to divide without them turning
into various retinal cell types. When a sufficient number of cells
has been obtained, the conditions are changed such that the cells
mature to form photoreceptor cells.
These exact conditions are difficult to define and finding the optimal
growth medium is a time consuming process. Our experiments have
progressed to the extent that we can grow up stem cells from various
mouse and pig eye tissues efficiently. These cells remain immature
and able to turn into a variety of cell types when the conditions
are changed. The next stage will be designing the methods to make
the immature stem cells differentiate specifically into photoreceptor
of stem cells
Normally, the differentiation of immature cells into
photoreceptor cells occurs only when the eye is formed in the embryo.
Over the years many groups have studied the circumstances under
which this occurs and we have a fairly good understanding of the
In order to
induce differentiation of stem cells to photoreceptor cells, we
have two tools that we can use. Firstly, we can add certain chemicals,
called growth factors, which are present during the development
of the eye. Many different growth factors exist and the combination,
timing and amount will affect the efficiency of photoreceptor formation.
A combination of recreating the mix of growth factors in the eye
and trial and error may lead us to the find the optimal conditions
Secondly, we can use genes to trigger the differentiation to photoreceptors.
Genes are encoded messages that tell the cell to perform a specific
task. A more detailed description of ‘genes’ is given
here. During the development of the retina, specific genes become
active to force the cells to become immature retinal cells; later
other genes cause them to become specific retinal cell types, such
as photoreceptors. From previous research, we have a good understanding
of which genes are involved in these processes. If we can temporarily
activate the correct gene or combination of genes, we should be
able to induce the differentiation to photoreceptor cells.
it is likely that a combination of growth factors and genes is required
for the optimal efficiency of photoreceptor differentiation.
This page last modified
18 December, 2012