Investigators at St. Jude Children’s Research Hospital have found that cells isolated from the eye that many scientists believed were retinal stem cells are, in fact, normal adult cells.
“The first clue that these cells were not stem cells was that they were pigmented,” says Michael Dyer, Ph.D., a member of the St. Jude Department of Developmental Neurobiology. “Neural stem cells, in general, and retinal progenitor cells, in particular, are not pigmented. Nevertheless, the previous finding was met with a tremendous amount of enthusiasm because of the promise of introducing these cells into the eye to regenerate photoreceptors lost to blindness.”
In 2000, scientists proposed that the layer of ciliary epithelial cells lining the inside of the eye contained retinal stem cells. They said that these cells formed tiny spheres of about a thousand cells when grown in culture dishes, and the spheres could be cultured to give rise to more spheres, reminiscent of the capabilities of stem cells. The cultured sphere cells also showed activation of genes characteristic of adult eye cells.
To repudiate those previous claims, the current researchers analyzed the sphere-forming cells in detail to determine whether they were really retinal stem cells. Studies of each cell in the spheres revealed all were pigmented and had features of ciliary epithelial cells.
In the article, which was published March 30 in the online early edition of the Proceedings of the National Academy of Sciences, the researchers also compared the structure of the sphere-forming cells with those of confirmed stem cells and other immature cells in the developing retina called progenitor cells.
That comparison revealed fundamental differences between the sphere-forming cells and established stem or progenitor cells. The researchers also found that simply culturing the sphere-forming cells in the same growth medium as is used for stem cells caused them to activate genes characteristic of stem cells yet remain adult ciliary epithelial cells.
Though the previous posits have been overturned, Dr. Dyer says that a particularly promising alternative is the possibility of taking samples of adult cells such as fibroblasts that form connective tissue from a patient with retinal degeneration and exposing them to genetic cues that induce them to revert to stem cells. Those induced pluripotent stem cells could then be manipulated to develop into light-sensing photoreceptor cells that could then be transplanted into the patient’s eyes to restore vision.
“This approach would solve many problems of developing cell-based therapy for blindness,” says Dr. Dyer. “First, these cells are immortal, so they can be grown indefinitely to produce large amounts of cells for treatment. And secondly, they would be immunologically matched to the patient, so there would be no danger of rejection. And thanks to some excellent research during the past 15 years, we know a lot about how to reprogram such stem cells to make them into photoreceptors.”