Embryonic stem cells are derived from human embryos, can only grow in culture indefinitely, and have the ability to potentially differentiate into any adult cell type in the human body. Because cell and tissues made from embryonic stem cells bear the same tissue types as the embryos from which they were derived, they will be rejected by the immune system patient. However, there are sites in our bodies were the immune system does not go, and that includes the central nervous system and the eyes. This is the reason why clinical trials with embryonic stem cell-derived cells have focused, to date, on spinal cord injuries and eye diseases.
Several clinical trials have examined the ability of retinal pigmented epithelial (RPE) cells made from embryonic stem cells to treat patients with dry macular degeneration or an inherited eye disease called Stargardt’s disease. Data from these trials has been reported in an article in the medical journal The Lancet, and accordingly, none of the treated patients showed tumor formation or immunological rejection of the implants and, most impressively perhaps, partial blindness was reversed in about half of the eyes that received transplants.
The results might re-energize the quest to harness embryonic stem cells for human medicine. Dr. Anthony Atala of the Wake Forest Institute for Regenerative Medicine called the work “a major accomplishment” in an accompanying commentary on the article.
RPE cells lie just behind the photoreceptor cells in the retina of our eyes. Photoreceptors have their ends hurried in the RPE layer. This arrangement exists for a very good reason; the photoreceptors are exposed to high intensities of light and they suffer respectable amounts of oxidative damage. The components of the photoreceptors cells are made in the very lowest parts of the RPEs and then are eventually pushed to the ends of the cells. At the end of the photoreceptor cells, the RPEs relieve the photoreceptors of their photodamaged parts and gobble them down, and recycle the cellular components. Thus, RPE cells serve a photoreceptor cell repair and service cells. If the RPE cells begin to die, the photoreceptors are not long the this work either.
In the case of dry macular degeneration, which accounts for 90 percent of diagnosed cases of macular degeneration, the light-sensitive photoreceptor cells of the macula (the portion of the retina were the day vision is the sharpest) slowly break down. Damage to the macula causes blurring or spotty loss of central vision and yellowish cellular deposits called drusen (extracellular waste products from metabolism) form under the retina between the retinal pigmented epithelium (RPE) layer and a basement membrane called Bruch’s membrane, that supports the retina. An increase in the size and number of drusen is associated with the death of RPE and, consequently, photoreceptor cells, and is sometimes the first sign of dry macular degeneration.
Mutations in several genes have been identified in families with dry macular degeneration that increase the risk for dry macular degeneration. These include the SERPING1 gene, those genes that encode the complement system proteins factor H (CFH), factor B (CFB) and factor 3, and fibulin-5. Additionally, some environmental and behavioral factors also influence the risk a person will develop macular degeneration. These include smoking, exposure to blue light, ingestion of a high-fat diet, elevated blood pressure and serum cholesterol levels, and low vitamin D levels.
Stargardt’s disease is an inherited, juvenile form of macular degeneration that is caused by mutations in the ABCR gene. The protein encoded by this gene is a waste metabolite transporter, and defects in this protein cause the build up of a toxic metabolite called lipofuscin in the RPE cells, which leads to their demise and the death of the photoreceptors.
In this study, the main goal was to assess the safety of the transplanted cells. The study “provides the first evidence, in humans with any disease, of the long-term safety and possible biologic activity” of cells derived from embryos, said co-author Dr. Robert Lanza, chief scientific officer of Advanced Cell Technology, which produced the cells and funded the study.
Nine patients with Stargardt’s disease and nine with dry age-related macular degeneration received implants of the retinal cells in one eye. The other eye served as a control. Four eyes developed cataracts and two became inflamed, probably due to the patients’ age (median: 77) or the use of immune-supressing transplant drugs.
The implanted RPE cells survived in all 18 patients, most of whose vision improved. In those with macular degeneration, treated eyes saw a median of 14 additional letters on a standard eye chart a year after receiving the cells, with one patient gaining 19 letters. The untreated eyes got worse, overall. The Stargardt’s patients had similar results.
In real-life terms, patients who couldn’t see objects under 12 feet (4 meters) tall can now see normal-size adults.
The vision of one 75-year old rancher who was blind in the treated eye (20/400) improved to 20/40, enough to ride horses again, Lanza said. Others became able to use computers, read watches, go to the mall or travel to the airport alone for the first time in years.
While calling the results “encouraging,” stem cell expert Dusko Ilic of Kings College London, who was not involved in the work, warned that even if the larger clinical trial planned for later this year is also successful, “it will take years before the treatment becomes available.”
Other cell types can also form RPE cells and these include induced pluripotent stem cells, mesenchymal stem cells from fat (Ophthalmic Res. 2012;48 Suppl 1:1-5), adult retinal stem cells (Pigment Cell Melanoma Res. 2011 Feb;24(1):233-40), and iris pigmented epithelial cells (Prog Retin Eye Res. 2007 May;26(3):302-21). We do not need to destroy embryos to treat eye diseases with stem cells.