Engineering Adult Stem Cells to Cure Blind Mice
University of Florida researchers were able to program bone marrow stem cells to repair damaged retinas in mice, suggesting a potential treatment for one of the most common causes of vision loss in older people.
The success in repairing a damaged layer of retinal cells in mice implies that blood stem cells taken from bone marrow can be programmed to restore a variety of cells and tissues, including ones involved in cardiovascular disorders such as atherosclerosis and coronary artery disease.
"To our knowledge, this is the first report using targeted gene manipulation to specifically program an adult stem cell to become a new cell type," said Maria B. Grant, M.D., a professor of pharmacology and therapeutics at UF's College of Medicine. "Although we used genes, we also suggest you can do the same thing with drugs — but ultimately you would not give the drugs to the patient, you would give the drugs to their cells. Take the cells out, activate certain chemical pathways, and put the cells back into the patient."
In a paper slated to appear in the September issue of the journal Molecular Therapy, scientists describe how they used a virus carrying a gene that gently pushed cultured adult stem cells from mice toward a fate as retinal cells. Only after the stem cells were reintroduced into the mice did they completely transform into the desired type of vision cells, apparently taking environmental cues from the damaged retinas.
After studying the cell-transformation process, scientists were able to bypass the gene manipulation step entirely and instead use chemical compounds that mirrored environmental conditions in the body, thus pointing the stem cells toward their ultimate identities as vision cells.
"First we were able to show you can overexpress a protein unique to a retinal cell type and trick the stem cell into thinking it is that kind of cell," said Grant, who collaborated with Edward Scott, Ph.D., the director of the Program in Stem Cell Biology and Regenerative Medicine at UF's McKnight Brain Institute. "As we proceeded, we found we could activate the stem cells by mimicking the body's natural signaling channels with chemicals. This implies a whole new field of stem cell research that uses drug manipulation rather than genetic manipulation to send these immature cells along new pathways."
Scientists chose to build retinal pigment epithelial cells, which form the outer barrier of the retina. In addition to being very specialized and easy to identify, RPE cells are faulty in many retinal diseases, including age-related macular degeneration, which affects nearly 2 million people in the United States, and some forms of blindness related to diabetes.
"This work applies to 85 percent of patients who have age-related macular degeneration," Grant said. "There are no therapies for this devastating disease."
The work was supported by the National Eye Institute. Researchers removed blood stem cells from the bone marrow of mice, modified the cells in cultures, and injected them back into the animals' circulatory systems. From there, the stem cells were able to home in on the eye injury and become retinal cells.
At 28 days after receiving the modified stem cells, mice that had previously demonstrated no retinal function were no different than normal mice in electrical measures of their response to light.
Grant and UF have patented some technology involved in the research.
A long-term study by Italian researchers shows that stem cells can help restore vision in eyes that have been blinded by burns. Moreover, the restored vision remained stable over 10 years.
Patients whose eyes have suffered heat or chemical burns typically experience severe damage to the cornea -- the thin, transparent front of the eye that refracts light and contributes most of the eye's focusing ability. The Italian technique uses stem cells taken from the limbus, the border between the cornea and the white of the eye, to cultivate a graft of healthy cells in a lab.
During the 10-year study, the researchers implanted the healthy stem cells into the damaged cornea in 113 eyes of 112 patients. The treatment was fully successful in more than 75 percent of the patients, and partially successful in 13 percent. Success was defined as an absence of all symptoms and permanent restoration of the cornea.Treatment outcome was initially assessed at one year, with up to 10 years of follow-up evaluations. The procedure was even successful in several patients whose burn injuries had occurred years earlier and who had already undergone surgery.
Current treatment for burned eyes involves taking stem cells from a patient's healthy eye, or from the eyes of another person, and transferring them to the burned eye. The new procedure, however, stimulates the limbal stem cells from the patient's own eye to reproduce in a lab culture. Several types of treatments using stem cells have proven successful in restoring blindness, but the long-term effectiveness shown here is significant. The treatment is only for blindness caused by damage to the cornea; it is not effective for repairing damaged retinas or optic nerves.
Chemical eye burns often occur in the workplace, but can also happen due to mishaps involving household cleaning products and automobile batteries.