Stem cell treatments hold tremendous hope for the future of biomedicine.

Experts have identified stem cell therapies as our best bet to remedy an array of degenerative conditions that are considered untreatable. The problematic hurdle that’s foiling the effectiveness of these treatments is navigating the logistics of keeping those stem cells alive long enough to make a long-lasting impact.

But we could be making headway in that regard.

Researchers from the Buck Institute have seemingly solved the pluripotent puzzle, reporting long-term restoration of vision in blind mice via stem cell regenerative therapies.

Publishing their findings in Cell Stem Cell, the Buck team used transplanted photoreceptors, taken from human stem cells, to block the immune response that rejects transplanted cells by the recipient, buying time for the stem cells to go to work.

IMPROVING STEM CELL THERAPIES

Not only is this a breakthrough in degenerative conditions – blindness has always been seemingly impossible to reverse – but highlights a significant step forward in stem cell regenerative therapy efficiency.

As mentioned, the glaring obstacle in stem cell treatment is keeping the stem cells functioning long enough to take a permanent effect. This blindness study represents large strides in that regard, as the Buck researchers managed to elude the immune system’s rejection of transplanted cells.

“This turned into a nice story of long-term restoration of vision in completely blind mice,” said Buck faculty and senior author Deepak Lamba, PhD, MBBS.

“We show that these mice can now perceive light as far out as nine months following injection of these [stem] cells.”

While the clinical trials on mice are encouraging, human response will be the real test. The findings do support vision restoration in humans through the same process: taking photoreceptors from human stem cells, and integrating them into the blind eye.

PHOTORECEPTORS & HOW STEM CELLS CAN RETURN VISION

When a person is suffering from a degenerative eye disease, it’s commonly characterized by a loss of photoreceptors. Photoreceptors are specialized neurons in the retina, converting light into signals for our brain to interpret, creating ‘sight’.

Human embryonic stem cells (ESC) are a source of photoreceptor replacements, as they possess the uncanny ability to differentiate into any human cell type.

Lamba’s preliminary work, while plausibly proving photoreceptors in mice could restore vision, held no evidence it was a sustainable treatment. A major controversy in the study, says Lamba, was the photoreceptors dying off quickly, or immediately rejected by the immune system, despite the eye and brain being areas the immune system doesn’t usually monitor.

So they went about solving that final barrier: finding a way to suppress the immune system’s rejection, long enough for the photoreceptors to integrate into a person’s visual system.

HOW’D THEY DO IT?

In the trials, the Buck Institute employed a specific strain of mouse that’s healthy, but lacks a certain immune cell receptor – one responsible for rejecting foreign cells (immunodeficient IL2 receptor gamma (IL2rl)).

“This mouse strain is 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,” said the publication’s lead author, Jie Zhu, PhD.

The researchers’ speculations were accurate: by side-stepping the immune system rejection, the Buck team documented a 10-fold increase in living, human embryonic stem cells that managed to mature and integrate with the retina.

Now that the longevity & integration of the transplanted cells was confirmed, they then had to see if the cells actually worked.

They replicated the process with another strain of mouse, one that’s congenitally blind. They discovered that even after nine months since the transplant, the mice’s eyes were responsive to light and messages from the brain.

“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,” said Lamba.

“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.”

NEXT STEPS

Like any zealous researcher, Lamba is happy with the results, but is far from content. He already has his team refining their work; one idea is to use drugs that’re used to prevent rejection for organ transplants, which target the same sight receptor.

“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,” Lamba continued.

“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.”

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