Stem Cells Restore Long-Term Vision in Mice Using Regenerative Vision Therapy

Oeil et test de visionStem cell therapies offer great potential for repairing function in a range of degenerative conditions. In a recent study, scientists restored vision in blind mice to support tackling the immune system’s function in denying transplanted cells.


Scientists working on the generation and transplantation of retina stem cells have seen success in one experiment – retina stem cells derived from an adult mouse.


Making certain that transplanted cells can survive long enough to work is one of the most common encounters in developing stem cell therapies. But now researchers have reported one of the first examples in improving longevity of functionally integrated stem cells and hampering the immune response that triggers the rejection of transplanted cells.


The good news? This incredible discovery holds great promise for bringing back function in a whole host of degenerative conditions, however, one of the strategic difficulties is how to make sure the cells survive in the body long enough to work.


By transplanting photoreceptors originating from human stem cells, researchers from the Buck Institute could demonstrate long-term vision restoration in mice by stopping the immune response that prompted patients to reject transplanted cells.


One of the crucial topics that needs to be tackled to enhance stem cell regeneration therapy productivity is immune system rejection, as published in the Cell Stem Cell.


These promising results support a means to developing scientific therapies, mainly for bringing back human vision through enabling photoreceptors emanating from human stem cells to amalgamate and develop in the eye.


As declared by Buck faculty and senior author Deepak Lamba, PhD, MBBS, “This turned into a nice story of long-term restoration of vision in completely blind mice. We show that these mice can now perceive light as far out as nine months following injection of these cells.”


Specialised neurons in the retina, photoreceptors alter light into signals that the brain translates as sight. A decline in these cells is a typical cut-off point in progressive eye diseases.


While human embryonic stem cells can offer a possible foundation for photoreceptor replacement, researchers hadn’t been able to demonstrate longstanding sustained vision restoration, even though Lamba’s previous work indicated that photoreceptors originating from stem cells could function in mice.


According to Lamba, one of the main controversies in this field is whether or not the transplanted photoreceptors merely perish or are vigorously eliminated by the immune system – the eye, together with the brain, had long been thought to be “privileged” in that the cells of the immune system didn’t monitor those locations.


The next step in Lamba’s research was to have the group carefully inspect the extent to which immune rejection adds to unsatisfactory results in stem cell therapies for the eye, and to ascertain if they could stumble upon a solution to the problem.


Supposing that rejection was happening and that it could be controlled, transplanted photoreceptors, they discussed, sprang from stem cells that may well have time to join into the visual system and start communicating information to the brain.


Using a specific mouse strain that was healthy but lacking in a specific immune cell receptor, the team discovered the mouse was unable to reject transplanted foreign cells. Named immunodeficient IL2 receptor gamma (IL2rl) null mice, these creatures lack the IL2ry receptor that humans also have as part of a functional immune system.


According to the publication’s lead author, Jie Zhu, PhD, a postdoctoral researcher who started in Lamba’s lab three years ago, “This mouse strain is a great model for this research because they are otherwise healthy and normal, including in their vision, so it allows us to conduct studies focused on cell integration.”


The mice used in the team’s research proved that without the rejection process, there was a 10-fold rise in living human embryonic stem cell-derived donor retinal cells that matured and integrated into the retina.


Having witnessed a momentous, long-term improvement and having established that transplanted cells could integrate, the next stage was to investigate if the cells actually worked.


So the team then transplanted the stem cell-derived photoreceptors into a different strain of mouse, known as CRX null, which is genetically blind. The team calculated the pupils’ reaction to light and observed the brains’ visual reaction centres to illustrate that signals from the eye were moving to the correct parts of the brain.


Even nine months to a year following photoreceptor transplantation, the team discovered that eyes were responding to light and relaying sight messages to the brain.


Lamba confirmed, “That finding gives us a lot of hope for patients, that we can create some sort of advantage for these stem cell therapies so it won’t be just a transient response when these cells are put in, but a sustained vision for a long time. Even though the retina is often considered to be ‘immune privileged,’ we have found that we can’t ignore cell rejection when trying to transplant stem cells into the eye.”


Dedicated to the scientific applications of human stem cells, Dr. Lamba’s lab has a specific interest in recovering vision that has been jeopardised by progressive eye diseases, like macular degeneration. At present, Zhu and Lamba claim they’re improving the current work. One angle is to utilise already-approved drugs to counteract rejection for organ transplant that affect the same receptor.


Zhu proclaims that: “Using an antibody against this specific receptor means that the immune system might not need to be suppressed more generally, which can be very toxic.”


Lamba maintains that: “We can also potentially identify other small molecules or recombinant proteins to reduce this interleukin 2 receptor gamma activity in the body — even eye-specific immune responses — that might reduce cell rejection.” She goes on to say that: “Of course it is not validated yet, but now that we have a target, that is the future of how we can apply this work to humans.”

Stem Cells Ease the Pain of Spinal Cord Injuries in Mice

A recent study at the University of California, San Francisco has found that neural stem cells can help alleviate the nerve pain and bladder issues caused by spinal injuries.

Patients who suffer spinal injuries often have to deal with numbness, loss of bladder control, and associated side effects of their paralysis. In part, this is due to overactive spinal cord circuits, which can cause pain and decrease quality of life.

In this particular study, a spinal injury was induced in mice, and two weeks later the stem cell treatments were tested. Instead of focusing on the site of the injury, researchers focused on areas where the spinal circuits were at their most active. These cells dispersed, and were integrated into the spinal cord. Because embryonic stem cells from humans rather than mice were used, this allowed them to see how the cells may act if the study is extended to human subjects.

By using a special paper in their cage lining, scientists were able to see where and how often the mice had urinated. After the treatment, the mice had fewer large spots, showing greater control over their bladders. They also showed signs of being in less pain, and exhibited less scratching behaviour – a chronic itch can be a side effect of spinal injuries.

Many patients with spinal injuries rely on a cocktail of drugs, from painkillers to antidepressants, as well as medicines to help them control their bladder. Unfortunately, each of these drugs comes with its own side effect, and they cannot always be relied on in the long term.

In the last few months, there have been several stories from across the world of stem cell treatments. Ajan Reginald, CEO of Celixir, compiled some of the highest profile updates in a recent blog post, and this included the story of a quadriplegic who had regained movement in his arms. While many of these stories focus on recovery from paralysis, the team at University of California, San Francisco are focused more on improving quality of life for spinal injury patients, and looking for alternatives to the usual prescription painkillers.

Stem Cells Repair Damaged Mouse Brain

2bf872ea-8e7d-4738-a859-f7b7d687fb07A recent study has used stem cells to repair damaged mouse brains, and this could give hope to stroke patients and those with other neurological conditions.

Lead by professors from the University of Southern California, the study is part of an ongoing effort to find ways to use stem cells on patients whose brains have been damaged by strokes and similar conditions. This particular experiment involved repairing the brain by creating new neurons, which was achieved by identifying damaged areas, and grafting healthy, human skin cells onto them.

Another method that was used involved creating a compound called 3K3A-APC.  When added to neural stem cells in a petri dish, this protein allowed stem cells to grow into neutrons. Although the experiment was carried out with animal brains, it may later be developed into a treatment suitable for humans. Researchers found that combining this protein was more effective than stem cell treatment alone, and created more ‘functional connections’.

To stimulate the effects of a stroke, researchers cut off blood flow to certain areas of the mice’s brains, and then allowed the damage to develop over a week. In human terms, this would be the equivalent of having a stroke and not seeking treatment for several months, with late treatment often making the effects of a stroke so much worse.

Stem cell research has long tried to help stroke victims, especially those whose outlook has been bleak in the past. Back in June, we reported that a study at Stanford’s University School of Medicine had seen amazing results with wheelchair bound patients who were injected with stem cells. This particular study even saw people confined to wheelchairs being able to walk again, while others reported greatly improved mobility.

The treatments pioneered in the Stanford study involved injecting infant stem cells, which helped damaged areas ‘reset’ themselves, and start to heal. Therefore, there could be many ways in future that stem cells might be used to improve the lives of stroke victims.

In addition to those suffering strokes, recent stem cell studies have also looked at treating those with degenerative conditions that otherwise might not have had hope in the past. Illnesses such as Alzheimer’s and Lou Gehrig’s disease see sufferers deteriorate over time, with very little in the way of treatments that can be offered. However, if stem cells have the potential to help stroke victims, then breakthroughs for other conditions could be close behind.

Companies such as Celixir Ltd, headed by CEO Ajan Reginald are undertaking clinical trials for many pioneering stem cell treatments. This includes treatments for individuals with heart disease and the repair of damaged tendons.

Will Brexit Affect the UK’s Stem Cell Research?

On the 24th June, the UK made the historic decision to leave the EU, and many industries are still waiting to see how this will impact them. Some of the scientific community reacted quickly and with gloom, with the former EU science advisor Anne Glover telling Science Mag that she was ‘very pessimistic’. While it’s still early days, and difficult to predict what will happen in the long term with regards to stem cell research, here are a few areas that might be affected.


The European Research Council provides funding across the EU to a wide variety of research projects. For the period of 2014-2020, the ERC’s budget is €13.1 billion, with 34% of that budget earmarked for life sciences, including Cellular and Developmental Biology. As it stands, the UK hosts more researchers with starting, consolidator, and advanced grants from the ERC than any other member state.

Leaving the EU doesn’t necessarily mean the UK will lose access to these grants, as people of any nationality can apply for them, but we may need to pay for inclusion. While we are currently a major beneficiary of the ERC, the UK could find themselves struggling, much like non-EU members Switzerland, for inclusion in further schemes.

Over at the Department for Business Innovation and skills, an unnamed official told the BBC that his team were looking at ways to fill in potential shortfalls. “They are trying to gather information on what are the areas of research that depend most on European funding and what the priority areas should be.”

Partnerships with the EU

Science minister Jo Johnson has provided a more positive picture of the effects of Brexit, and in speech given at the Royal Society of Biology he claimed that world-class research ‘will endure’, as we are still part of the European Research Area. His speech also covered the impact of leaving the EU on current students who may be studying science related subjects in the UK, stating that they would still receive student finance.

Others were less optimistic about the result and the impact it might have on research networks. Scientists for EU was set up to campaign for the remain side, and have been vocal about the impact that leaving will have on partnerships and research agreements. They have argued that even as an Associate Member of the EU, the UK might struggle to regain its current position in the ‘political union’.

EU scientists working in the UK

Immigration was a big talking point in the run up to the referendum, and leaving the EU could make it harder for scientists from abroad to work and study here. At the moment, there’s no immediate impact, but schemes such as Erasmus+, which is an exchange program for EU students, will have to be reviewed.

During the campaign for Britain to leave the EU, many in the pro-leave camp suggested a points based system. Therefore, those working in specialist professions such as scientists and researchers might fare better than unskilled workers.

Stem cell regulations

Different EU countries have different regulations when it comes to stem cells. For example, Germany and Italy have strict laws about the use of embryonic stem cells, while the UK has comparatively liberal laws. This means that the UK has become a leader in stem cell research, and UK scientists shouldn’t see their work disrupted by Brexit. However, it does mean that EU scientists who planned to carry out their research in the UK may struggle in future if restrictions on movement are put in place.

We may not know for a while what the long-term effects of leaving the EU will have on stem cell research, or scientific research in general. A report by the Commons Select Committee titled ‘Leaving the EU: implications and opportunities for science and research’ will be published in the coming months, and this should tell us more. Whichever way you look at it, there could be a period of uncertainty ahead in terms of stem cell research.

Wheelchair Bound Stroke Survivors Walk Again After Stem Cell Treatment

point to the imaging area. Doctor and CT-scan.

A stem cell study, based at Stanford University School of Medicine in California, has shown some incredible results in treating paralysed and wheelchair-bound stroke patients.

A small group of 18 patients underwent ground-breaking medical procedures in which a hole was drilled into their skull, with stem cells injected into certain damaged areas of the brain. Patients in the study included people whose strokes had occurred six months to three years before the procedure, as this is often regarded by doctors as being past the point where the brain can regenerate and heal itself.

By injecting stem cells into damaged areas of the brain, the theory was that the adult brain would ‘reset’ itself back to an infant brain, and could then start to heal from the trauma of a stroke. Children’s brains often heal well after a traumatic injury or event such as a stroke, and by using stem cells from donor bone marrow, researchers were able to make adult brains heal themselves in the same way.

The results were better than anticipated. Speaking to the Daily Telegraph, the Chair of Neurosurgery, Professor Gary Steinberg said:

““This wasn’t just ‘they couldn’t move their thumb and now they can’. Patients who were in wheelchairs are walking now. Their ability to move around has recovered visibly. That’s unprecedented.”

This simple procedure was carried out under local anaesthetic, with patients able to go home the next day. Short-term side effects were no more serious than a headache, and so far no long-term side effects have been noted. The injections were carried out two years ago, and since then none of the patients have had a relapse.

Not only does this procedure have the potential to help many stroke victims, who in the past may not have had much hope of recovery, but also those who have suffered life-changing brain injuries, and those suffering from neurodegenerative disorders such as Alzheimer’s, Lou Gehrig’s disease, and Parkinson’s. These conditions often see sufferers facing a bleak future, but stem cell therapy could offer them a ray of hope.

Could Stem Cell Therapy Be Used for Hard to Treat Angina Patients?

stem cellA recent study by the Society for Cardiovascular Angiography and Interventions (SCAI) in Orlando, Florida has shown that stem cell therapy could potentially be used to ease refractory angina; a previously difficult to treat condition.

Refractory angina (RA) is an increasingly common illness that is estimated to affect around a million Americans. RA is caused by severe blockages in the heart, which restrict blood flow and cause life-limiting issues such as chest pains, tiredness, dizziness, and a shortness of breath. Unlike many other types of angina, refractory angina isn’t responsive to the usual treatments such as lifestyle changes, surgery, and medication.

Test subjects in the trial were transplanted with CD34+ cells which were self-donated. These cells were chosen as previous studies had shown that patients with coronary artery disease had a better outcome if the CD34+ levels in their bone marrow were high. Out of 112 patients studied in the trial, 57 of them received CD34+ cells, while the others received a placebo.

In follow up sessions at three, six, and 12 months, it was found that patients who had received the stem cell treatment were able to exercise for longer, and that their risk of a major angina attack had decreased.

At the two year follow up, it was found that patients who had received the stem cells had a lower rate of mortality.

The study found that the positive effects of stem cell therapy tended to decrease over time, which would mean that if this kind of therapy would need to be administered regularly.

SCAI unfortunately had to cut the study short due to funding issues, and although the original plan was to see 444 patients with refractory angina, only 112 were used in the trial. However, the results could be an exciting step towards creating better therapy for patients with difficult to treat heart conditions.

Disease specific and tissue specific stem cell therapy will save and transform lives around the world

Stem Cell Therapy is extremely promising in terms of being able, in the future, to cure failed organs. Stem cells can help us to understand and treat different diseases, injuries and health related problems.

Presently, the most common use of stem cell therapy is the transplantation of blood stem cells to treat diseases and conditions of the blood and immune system, or to rejuvenate the blood system following treatments of certain cancers. Currently, more than 26,000 patients are treated with blood stem cells in Europe every year.

Also, the skin. Skin stem cells have been successfully used to grow skin grafts for patients that have suffered from severe bodily burns. At the moment, the burns would need to be life-threatening before the option of stem cell therapy is used. There is still a way to go with this and scientists are continuing their research into skin stem cells since the new skin currently has no hair follicles and cannot sweat.

Furthermore, the recent conditional approval in Europe of Holoclar, means that stem cells can be used to repair damage to the surface of the eye after an injury such as a chemical burn.

Other applications of stem cells to treat different parts of the body are continuing to be explored and it can take years for them to be thoroughly investigated, approved and ready for market, following all the necessary clinical trials.

Ajan Reginald, Executive Director of Cell Therapy Ltd and Nobel Prize Winner Professor Sir Martin Evans are dedicated to using stem cells to develop life-saving and life-altering regenerative medicines. Whereas most stem cell companies follow a philosophy of having one cell that can treat all diseases, Ajan Reginald and Professor Sir Martin Evans have discovered disease-specific and tissue specific progenitor cells and have invented targeted regenerative medicines from these cells.

So far, two such medicines have both passed stage II of clinical trials; Heartcel, to repair broken hearts and Tendoncel, to regenerate injured tendons near the surface of the skin.

Stem cells are the body’s master cells. Unlike other cells, stem cells can turn into almost any other cell in the body. If these new medicines prove to work, they could revolutionise the way we treat disease and could save and transform the lives of billions of people around the world.