Blind People Offered Hope of Seeing Again After Stem Cell Breakthrough Remakes Retinal Blood Vessels

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Blind people have been offered fresh hope of seeing again after lab-grown cells restored retinal function in mice.

When injected into mice with retinal disease, the special retinal blood cells integrated into the damaged tissue to regenerate blood vessels and restore retinal function—including in a model of the leading cause of vision loss in working-age people.

The experiment was conducted by biomedical engineers at Duke University, North Carolina, and saw the use of induced pluripotent stem cells (iPSCs) to grow specialized blood vessel cells critical to retinal health for the first time.

Shinya Yamanaka won the Nobel Prize in 2012, which he shared with Sir John Gurdon, for discovering the now-termed “Yamanaka factors” that could ‘induce’ a normal adult cell back into a stem cell that could be remade into any cell in the body: hence the name ‘pluripotent’ stem cell.

The Duke research team also demonstrated the iPSCs’ ability to form functional retinal vascular tissue in a lab-grown environment, providing a pathway for future research into various eye diseases.

“Retinal vascular diseases affect millions of people, but our understanding remains limited, hindering our ability to discover and develop new therapeutics,” said Professor Sharon Gerecht, who led the research published in the journal Nature Biomedical Engineering.

“Using human stem cells, we generated the cells found in retinal blood vessels, paving the way for new therapeutic approaches.”

The retina extends directly to the brain, technically making the eyes part of the central nervous system. Also like the brain, the retina has a blood barrier that strictly controls what goes in and out such as oxygen, nutrients, water, and pharmaceuticals.

While the barrier of retinal endothelial cells keeps the retina healthy and relatively protected from disease-causing agents, Gerecht says it also makes treating the retina difficult.

“When this specialized blood vessel tissue begins to break down, it can cause a lot of different diseases that lead to vision loss,” said study first co-author Parker Esswein, a PhD student working in the Gerecht lab. “While there are sources of retinal endothelial cells, being able to grow a continuous supply from scratch could offer many advantages for those working in the field.”

The retinal endothelial cells are currently collected and grown from real patients, making them relatively expensive with a limited supply. To expand access, reduce cost and control variability, the Gerecht lab wanted to see if they could grow them from iPSCs.

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The research team took commercial iPSCs and used a well-established procedure to get them to grow into common endothelial cells which form the inner layer of most of the body’s blood vessels.

The researchers then used a specialized cocktail of growth factors to coax the cells into becoming the specific type of endothelial cells found in the retina. Once successful, the researchers put their new creations to the test.

In experiments, the team was able to get the cells to form the same networks and structures that they do within the body. Next, the researchers subjected the lab-grown tissues to low oxygen and high glucose levels, which are detrimental conditions often seen in real people with diabetes.

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The team explained that the conditions are “fundamental” triggers of diabetic retinopathy, the leading cause of vision loss in working-age people in the United States, and caused the tissue barrier to break down just like it does in patients.

The researchers then tried their lab-grown cells as a therapy for mouse models. When injected into the mice before any actual vision loss occurred, the cells successfully integrated into the existing tissue and helped develop strong blood vessels with strong barriers.

“The tests showed that these lab-grown cells have promise for preventative treatments, especially since they should be easier and cheaper to obtain using our technique,” said Esswein.

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“While our benchtop experiments did not attempt to model a wide variety of specific eye diseases in these studies, we’re confident we can create excellent human tissue models in the lab to help better understand these diseases and uncover therapies.”

Now the research team is planning to explore potential uses for their retinal endothelial cells both in their laboratory and through emerging industry partnerships. The group also has a patent pending that covers both the stem cell-based therapeutics and in vitro modelling for drug discovery and testing.

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