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In people with severe eye disease, transplants made from embryonic stem cells (in region of black dotted circle) appear safe, and became larger and more pigmented over time (right).

In people with severe eye disease, transplants made from embryonic stem cells (in region of black dotted circle) appear safe, and became larger and more pigmented over time (right).

S. D. Schwartz, et al., The Lancet, Online publication (October 15, 2014)

Stem cell therapy seems safe for severe eye disease

Eighteen adults with severe eye disease who were among the first people to receive transplants created from human embryonic stem cells (hESCs) continue to have no apparent complications with the introduced cells after an average of nearly 2 years, according to the latest status report on their health. Vision tests also suggest the eyesight of more than half of the subjects has improved, but other researchers expressed caution about those results. Nevertheless, the outcome may pave the way for transplants of stem cell–derived eye cells called photoreceptors, which could dramatically improve vision in people with eye disease if all goes according to plan.

Eye diseases—such as age-related macular degeneration, as well as a genetic condition called Stargardt’s macular dystrophy that afflicts young people—are considered excellent candidates for stem cell therapy because the eye is an immune-privileged site, meaning transplanted cells are not as likely to be rejected as foreign compared with transplants elsewhere. (Volunteers in these trials nonetheless received immunosuppressants for 12 weeks as a precaution.) Such treatment could, in theory, repopulate the eye with cells that have been destroyed, helping restore lost sight. But there are many hurdles: Among them, growing enough of the cells in a petri dish and ensuring that they connect to “the existing machinery” in the eye, says Hendrik Scholl, who co-directs the Center for Stem Cells and Ophthalmic Regenerative Medicine at Johns Hopkins University in Baltimore, Maryland. There have also been safety concerns confronting all hESC studies, including worries that the embryonic stem cells could proliferate out of control.

Today’s report, which appears in The Lancet, follows on another from the same group in early 2012. Then, a team led by Robert Lanza, the chief scientific officer of Advanced Cell Technology Inc. in Marlborough, Massachusetts, and his colleagues published the first results ever of a clinical trial using human embryonic stem cells. That study reported that the first two patients treated, both of them legally blind, had suffered no ill effects from the cells.

Now, Lanza and Steven Schwartz, who heads the retina division at the Jules Stein Eye Institute at the University of California, Los Angeles, along with their colleagues, share more details from early studies in two different eye diseases. They describe outcomes on nine people with age-related macular degeneration and nine with Stargardt’s. The volunteers, ranging in age from 20 to 88, received injections under their retina of a particular type of eye cell, retinal pigment epithelium (RPE) cells, which were derived from hESCs in the lab. RPE cells have some big advantages for initial hESC safety studies: Because they are pigmented, they can be tracked. They are also relatively easy to grow, manipulate, and control in the lab. The downside is that people with these eye diseases are losing sight in large part because they’re losing a different type of eye cell: the photoreceptors that sense light in the retina.

Still, the trial results offer hope so far. After the surgery, 13 of 18 patients had an increase in pigmentation, suggesting that the transplanted cells were doing their job. The authors also reported that 10 patients described some improvement in their vision, which Lanza says was an unanticipated result. “In the best-case scenario, we thought we could hopefully prevent the loss of vision in these patients,” he says, because RPE cells are known to help maintain existing photoreceptors, in part by digesting the cellular debris that they shed. “We never really expected such dramatic improvement,” Lanza says. He suspects that transplanted cells are actually restoring the function of “dormant” photoreceptors.

However, the improvements didn’t correlate with how much additional pigment researchers detected, and Lanza is careful to point out that for ethical reasons, the study had no control group that received the surgery without the transplanted cells.

Scholl is upbeat that the transplanted cells still appear safe and says that analysis of the cells in the recipients’ eyes are “indeed an indication that something is happening.” The “small signal” that vision improved in this cohort could be because the remaining photoreceptors “are exposed to a healthier environment,” he believes. Or it could be due to the cataract surgery several patients in the study received, or the challenges of measuring vision to begin with. Still, Scholl adds, transplantation of RPE cells “can’t be it” for such patients, because ultimately they need new photoreceptors to restore vision.

Some groups, including Lanza’s, are looking to do just that: transplant photoreceptor cells. Initial evidence shows that these cells, derived from hESCs, have “an amazing capacity” to migrate into the retina and restore vision, Lanza says. But they’re more difficult to grow in the lab, and testing is right now limited to animals. In the long term, it’s hoped that injecting these cells could make a dramatic difference for people whose sight is disappearing or has already vanished.