Despite many animal studies over 30 years, there have been no assessments of the long-term safety or effectiveness of hESCs in humans.
Since 1981, when pluripotential cell cultures were first derived, human embryonic stem cells (hESCs) have been considered to be a potential source of cells to treat diseases caused by tissue loss or dysfunction.
However, scientists were concerned that the self-renewing abilities of these cells could lead to tumor development or other problems.
Despite plenty of animal studies over the past 3 decades, there have been no assessments of the long-term safety or effectiveness of hESCs in humans.
"Embryonic stem cells have the potential to become any cell type in the body, but transplantation has been complicated by problems including the risk of teratoma formation and immune rejection," explains lead author Prof. Robert Lanza, chief scientific officer at Advanced Cell Technology in Marlborough, MA.
"As a result," Lanza adds, "immunoprivileged sites (that do not produce a strong immune response) such as the eye have become the first parts of the human body to benefit from this technology."
Across two studies, hESCs were transplanted into 18 patients with severe vision loss. Nine of the patients had atrophic age-related macular degeneration and nine had Stargardt macular dystrophy - these conditions eventually cause complete blindness and there are no effective treatments for them.
The participants were injected with a dose of either 50,000, 100,000, or 150,000 retinal cells under the retina in their eye that had the worst vision.
hESC-derived cells were 'well tolerated' with no safety concerns
The researchers found that the hESC-derived cells were well tolerated for up to 37 months after transplantation. During a median follow-up of 22 months, the researchers found no safety concerns.
Some adverse events were associated with surgery and immunosuppression, but the researchers say that these events were not related to the hESC-derived cells.
Follow-up testing in the first year after transplant demonstrated that eight of the patients were now able to read over 15 additional letters. In seven patients, visual acuity remained the same or improved. One patient, however, reported a decrease in visual acuity by more than 10 letters.
Overall, 10 out of 18 treated eyes had substantial improvements in how well they could see, and untreated eyes did not show any similar visual improvements.
"Our results suggest the safety and promise of hESCs to alter progressive vision loss in people with degenerative diseases and mark an exciting step towards using hESC-derived stem cells as a safe source of cells for the treatment of various medical disorders requiring tissue repair or replacement," says co-lead author Prof. Steven Schwartz, from the Jules Stein Eye Institute in Los Angeles, CA.
In a linked comment, Anthony Atala, director of the Wake Forest Institute for Regenerative Medicine, Wake Forest School of Medicine, Winston-Salem, NC, writes:
"The work by Schwartz and colleagues is a major accomplishment, but the path to get to this point has not been smooth. Since the discovery of hESCs in 1998, much has transpired, including political, ethical, and scientific debates, with an overall push to achieve the promise of human therapies. Now, we have follow-up that extends to longer than 3 years in patients treated with hESC-derived stem cells, showing both safety and apparent efficacy.
Much work remains to be done before hESCs and induced pluripotent stem cell therapies go beyond regulatory trials, but the path is now set in motion."
Recently, researchers at the University of Southampton in the UK published a study in PLOS ONE that found stem cells can be cultured from the eye, which may lead to improved treatments for blindness.