Three individuals with profoundly impaired vision who got stem-cell transplants have seen significant improvements in their eyesight that have lasted for more than a year, marking a significant advancement in the restoration of blind vision.
A fourth person with very compromised vision saw improvement, although it did not last.
These four are the first to receive transplants of reprogrammed stem cells to heal injured corneas, the eye’s clear outer surface.
The research was published on November 8 in the journal Nature.
Restoring vision
The findings, published in The Lancet today, are stunning, according to Kapil Bharti, a translational stem-cell researcher at the US National Eye Institute, National Institutes of Health, in Bethesda, Maryland. “This is an exciting development.”
“The results merit treating more patients,” says stem-cell researcher Jeanne Loring at Scripps Research in La Jolla, California.
The limbal ring, the dark ring around the iris, houses a reservoir of stem cells that keep the cornea’s outermost layer healthy.
When this vital source of rejuvenation is depleted—a disorder known as limbal stem-cell deficit (LSCD)—scar tissue forms on the cornea, eventually leading to blindness. LSCD can be caused by ocular damage as well as autoimmune and hereditary illnesses.
Treatments for LSCD are limited. They usually require transplanting corneal cells produced from stem cells extracted from a person’s healthy eye, which is an invasive process with questionable results.
When both eyes are afflicted, corneal transplants from deceased donors are an option; however, the recipient’s immune system may reject them.
Kohji Nishida, an ophthalmologist at Osaka University in Japan, and his colleagues made the corneal transplants using an alternative source of cells: induced pluripotent stem (iPS) cells.
They took blood cells from a healthy donor and reprogrammed them into an embryonic-like state, then transformed them into a thin, transparent sheet of cobblestone-shaped corneal epithelial cells.
Stem cell treatment
Between June 2019 and November 2020, the team enrolled two women and two men aged between 39 and 72 years old with LSCD in both eyes.
As part of the surgery, the team scraped off the layer of scar tissue covering the damaged cornea in only one eye, then stitched on epithelial sheets derived from a donor and placed a soft protective contact lens on top.
Two years after receiving the transplants, none of the recipients had experienced severe side effects. The grafts did not form tumors—a known risk of growing iPS cells—and did not show clear signs of being attacked by the recipients’ immune systems, even in two patients who did not receive immunosuppressant drugs.
“It is important and a relief to see grafts were not rejected,” says Bharti. But more transplants are needed to be certain of the intervention’s safety, he says.
After the transplants, all four recipients showed immediate improvements in their vision and a reduction in the cornea area affected by LSCD.
The improvements persisted in only one recipient, who showed slight reversals during a one-year observation period.
Bharti says it isn’t clear what exactly caused the vision improvements. It’s possible that the transplanted cells themselves increased in the recipient’s corneas.
However, the vision gains could also be due to the removal of scar tissue before the transplant or the transplant triggering the recipient’s cells to migrate from other eye regions and rejuvenate the cornea.
Nishida says they plan to launch clinical trials in March to assess the treatment’s efficacy. Several other iPS-cell-based trials are underway globally to treat eye diseases, says Bharti. “These success stories suggest we are headed in the right direction.”
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