by Dan Roberts
(Updated February 20, 2015)
Several studies are showing success at using stem cell transplantation to treat retinal degeneration. This article describes the progress of the research.
University of Washington
In 2006, a team from the University of Washington used a mix of “growth factors”, natural proteins that encourage cell growth, to coax embryonic cells into becoming retinal pigment epithelial (RPE) cells. It was the first use of human stem cells using the technique for the retina.
Researcher Tom Reh said his team had begun injecting the new cells into the eyes of retina-damaged mice, measuring nerve reactions to see whether there is actual vision improvement. Reh, along with Deepak Lamba, the lead author of the research report, and the UW team reported their findings in the August 2006 online version of the Proceedings of the National Academy of Sciences.
Advanced Cell Technology (Now owned by Acucela)
On September 21, 2006, Raymond D. Lund, (University of Utah’s John A. Moran Eye Center in Salt Lake City) and Robert Lanza (Advanced Cell Technology Inc. in Worcester, Mass.) reported that cells grown from human embryonic stem cells slowed vision loss when injected into the eyes of rats with a disease similar to macular degeneration.
According to a September 21, 2006 press release (“Stem Cell Experiments Slow Vision Loss in Rats” by Rick Weiss, Washington Post) the researchers achieved the transformation in all 18 stem cell lines they worked with, proving that their approach can consistently produce the crucial pigment cells. Then they injected the cells, about 20,000 per eye, into the retinas of 14 rats with a genetic disease similar to macular degeneration. Eight control rats received eye injections without any cells.
Forty days after treatment, the team measured retinal electrical activity in response to flashes of light, and it found that the treated rats were twice as responsive as the untreated ones, which by then were going blind. A separate test — which tracks eye and head movements in response to a moving display, a measure of an animal’s ability to discern fine details — showed that the treated rats had twice the visual acuity of the untreated rats nearly three months after treatment.
Microscopic examination of the retinas at autopsy showed that the treated eyes had healthy photoreceptor layers five to seven cells thick, while the untreated eyes had an average thickness of just one cell. (Healthy rats have layers 10 to 12 cells thick.) None of the cells divided abnormally or grew into tumors, the team reported in the September 2006 issue of the journal Cloning and Stem Cells.
In 2006, Advanced Cell Technology (ACT) announced success with a technique for harmlessly removing a single cell (a blastomere) from an eight-cell human embryo. In June 2007, announced successful production of a human embryonic stem cell line (hESC) without destroying an embryo. In November, 2010, the company announced that the FDA approved injection of human embryonic stem cells into the eyes of 12 patients affected by advanced cases of Stargardt disease, one of the most common forms of juvenile macular blindness.
On January 23, 2012, ACT reported preliminary results from the study, which involved one elderly patient with AMD and one younger patient with Stargardt disease. The study is by Dr Robert Lanza, Chief Scientific Officer at Advanced Cell Technology, Marlborough, MA, and Professor Steven Schwartz, Jules Stein Eye Institute Retina Division at the University of California, Los Angeles, CA, and their colleagues. As reported in the Lancet, the transplants appeared safe after four months, and both patients had some improvement in vision. Additional clinical trial sites have more recently been established at Wills Eye Institute in Philadelphia, Bascom Palmer Eye Institute in Miami, and Massachusetts Eye and Ear Infirmary in Boston.
Under their new name, Ocata Therapeutics, Inc., the company is working toward the start of Phase 3 in 2015.
Wake Forest University
On January 7, 2007, researchers at the Institute for Regenerative Medicine at Wake Forest University School of Medicine discovered another potential source of embryonic stem cells in the amniotic fluid that protects babies in the womb. These cells appear to be almost as malleable as those in the embryo itself, and the advantage would be that harvesting them would not harm the embryo. Several more years of study would be needed to assess their application in humans.
London Project to Cure Blindness
Other research is taking place in the United Kingdom at the University College London, Moorfields Eye Hospital and Sheffield University, in a cooperative effort called the London Project to Cure Blindness. Doctors at Moorfields have had some success with human subjects using adult stem cells from the patients’ own eyes. Embryonic cells, however, have been shown to be more malleable and easier to transplant than adult stem cells. Laboratory-grown cells from the blastocyst of a 5-day old embryo require only one injection (a 45-minute procedure), whereas the Moorfields experiments have taken two hours and two surgical procedures. This protocol would be very expensive and impractical in general practice, so the researchers at the University of Sheffield are using embryos, which will take a little longer to get into human trials.
On March 24, 2011, Georgetown University Medical Center reported in the journal “Stem Cells” that their researchers have, for the first time, produced retinal cells from human induced pluripotent stem (hiPS) cells, rather than embryonic stem cells. hiPS cells are derived from the patient’s own body, thus bypassing the moral issue of using human embryos.
This was an important step in the research, but, according to the study’s lead author Nady Golestaneh, Ph.D., assistant professor in GUMC’s Department of Biochemistry and Molecular & Cellular Biology, there were several viability and safety issues that still needed to be addressed before hiPS cells can be introduced into humans. These include rapid telomere shortening, DNA chromosomal damage and increased p21 expression that cause cell growth arrest.
RIKEN Center for Developmental Biology
On September 12, 2014, researchers at the RIKEN Center for Developmental Biology in Japan surgically transplanted into the eye of a woman a sheet of retinal pigment cells made from her own skin. This marks the first time stem cells from a person’s own body have been induced to become retinal cells and implanted into a human. Lead researcher Masayo Takahashi hopes these “induced pluripotent stem cells” will be a safer and more effective procedure than using stem cells created from a borrowed embryo.
It is important to remember that stem cell transplantation is a treatment, not a cure. It is definitely promising, but if the cause of the disease is not eliminated, even replacement cells can eventually be affected. The cure will likely come from gene replacement, and that is a few more years down the road.
More about stem cells:
A Primer on the Use of Stem Cells in Ophthalmology
The First Seven Years: An Overview of Stem Cell Transplantation Research for Treatment of Retinal Disease
by Dan Roberts