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A blog by the Gene and Cell Therapy Group at the UCL Institute of Ophthalmology Department of Genetics

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New Breakthrough: Transplantation of Photoreceptors from Retina Grown ‘in a dish’

PrateekBuch22 July 2013

Cover of Nature Biotechnology journal featuring our latest stem cell breakthroughThe UCL gene and cell therapy group, led by Professor Robin Ali, have carried out the first successful transplant of light-sensitive photoreceptor cells taken 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 findings, published today in Nature Biotechnology, suggest that embryonic stem cells could in future provide a potentially unlimited supply of healthy photoreceptors for retinal cell transplants 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 our team at UCL (University College London) 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, we were able to grow retinas containing all the different nerve cells needed for sight.

Commenting on the latest breakthrough, Professor Ali 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.”

We 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. We also carried out tests to look at the genes being expressed by the two types of cells to make sure they were biologically equivalent.

We 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. We 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 identifies critical steps needed to improve the success of cell transplantation and proves unequivocally that embryonic stem cells can provide a renewable source of photoreceptors that could be used to treat blindness.”

See news items on this research:

 

BBC: ‘Big leap’ towards curing blindness in stem cell study

Independent: Cells to restore eyesight are grown in lab and transplanted into blind mice

Daily Mail: Could cell transplant give sight to millions? Scientists grow retinas in the lab to create crucial connections to the brain

Guardian:Embryonic stem cells could help restore sight to blind

New Scientist:Eye receptor transplant promises therapy for blindness

Stem Cell Therapies for Sight Loss – How to Avoid Bogus Treatments

PrateekBuch4 February 2013

Stem cells – cells that have the capacity to turn into virtually any cell in the human body – are an exciting source of potential treatments for a huge range of medical conditions. Stem cells are already being used in the treatment of disorders of the blood. Academics, clinical specialists and companies throughout the world are developing treatments for other conditions, including many that cause sight loss. Our own group has begun testing the safety of transplanting retinal cells grown from stem cells in patients with Stargardt disease.

Unfortunately there are a number of ‘stem cell therapies’ that are being promoted as proven treatments, without scientific evidence or appropriate approval. Here we aim to help those considering stem cell therapy for sight loss to distinguish between the approved experimental techniques in clinical trials, and the bogus treatments being offered elsewhere.

It’s important to remember that no stem cell treatment has been approved for eye disease by the medical authorities. This is because clinical trials involving stem cells in the eye are at the very earliest stages, and it is too early to know whether their use is safe or effective. Until such trials are completed, any treatments on offer are likely to be unproven.

There are a number of clinics and companies that offer what they describe as stem cell transplants for a wide range of conditions, often at significant cost. These transplants have not been subject to the rigorous safety checks that are part of properly-conducted clinical trials. The clinics offering them are usually located in countries with less stringent standards of safety and regulations than we expect in the UK, enabling them to sell such treatments in the absence of published scientific evidence to support them.

The treatment typically involves the injection of stem cells (or rather cells that come from bone marrow, or the umbilical cords of newborn babies) without first turning them into a particular cell type. The difference between these cells and cells we are using in our clinical trial is a subject for another day, but for now it’s worth remembering that the cells in our studies are first made into retinal cells in a dish before being delivered into the eye. There is no evidence that stem cells injected into the body can reach the eye, or that once they do they can repair any damage. Furthermore, there is a very real possibility that such cells could cause harm by proliferating uncontrollably.

Turning stem cells into retinal cells in a dish

In our cell transplantation clinical trial we take stem cells and turn them into retinal cells in a dish – it is these retinal cells, not the stem cells themselves, that we inject. The injection of stem cells remains an unproven and potentially dangerous technique.

Companies offering these injections often feature patient testimonials, which are not a reliable indicator of safety or efficacy. The only reliable, peer-reviewed, published account of a patient receiving such transplants that we are aware of shows very clearly that there was no way to tell what kind of cells were injected, and that there was no effect whatsoever on vision after treatment.

In the absence of any scientific evidence supporting the direct injection of stem cells, we cannot recommend any of the treatments currently on offer. Should you be considering any such treatments, we strongly recommend that you check our Frequently Asked Questions and contact us first for advice.