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.”