A research team led by Raymond Lund, Ph.D., Professor Emeritus of Ophthalmology, and Trevor McGill, Ph.D., Research Assistant Professor at the Casey Eye Institute, Oregon Health and Science University have made a remarkable discovery using proprietary stem cells from StemCells, Inc. These results await publication in the European Journal of Neuroscience, and constitute positive preclinical data for StemCells, Inc. proprietary Human Central Nervous System Stem Cells (HuCNS-SC).
For these experiments, the team used Royal College of Surgeons (RSC) rats. RCS rats have an inherited form of retinal degeneration. Although the genetic defect that causes retinal regeneration was not known for many years, it was identified in the year 2000 to be due to a mutation in the Merkt gene. Mutations in the Merkt gene prevent the retinal pigment epithelium cells from scooping up outer segments of photoreceptor cells. As photoreceptor cells respond to light, their outer membrane proteins suffer photo-oxidation. Retinal pigment epithelial cells phagocytose these defective photoreceptor outer membrane segments and recycle them, which maintains photoreceptor health and function. When retinal pigment epithelium cells are unable to phagocytose photoreceptor out membrane segments, the photoreceptors accumulate photo-damage and eventually die.
To test the efficacy of HuCNS-SCs in preserving photoreceptor health, Lund and his colleagues injected HuCNS-SCs into the subretinal space of 21-day old RCS rats. They found that photoreceptors, the key cells of the eye involved in vision were protected from degeneration. Additionally, the density of healthy cone photoreceptors (those photoreceptors that help in color perception) remained relatively constant over several months. Visual acuity and luminance sensitivity tests in the injected RCS rats further corroborated the results of observed in the retinas. Apparently, the donor cells remained immature and did not differentiate throughout the seven-month experiment. However, the transplanted HuCNS-SCs underwent very little proliferation, and produced no tumors or abnormal growths. The ability of these transplanted cells to protect photoreceptors and preserve vision when injected into the retinas of RCS rats is important to human disorders of vision loss such as dry age-related macular degeneration (AMD).
Lund excitedly noted: “These results are the most robust shown to date in this animal model. One of the more striking findings is that the effect on vision was long-lasting and correlated with the survival of HuCNS-SC cells more than seven months after transplantation, which is substantially longer than other cell types transplanted into this same model. Also important, particularly for potential clinical application was that the cells spread from the site of initial application to cover more of the retina over time. These data suggest that HuCNS-SC cells appear to be a well-suited candidate for cell therapy in retinal degenerative conditions.”
Another investigator in this study, Alexandra Capela, Ph.D., a senior scientist at StemCells, commented, “This study showed that the HuCNS-SC cells persisted and migrated throughout the retina, with no evidence of abnormal cell formation, which supports our hypothesis of a single transplant therapeutic. With this research, then, we have shown that vision can be positively impacted with a simple approach that does not require replacing photoreceptors or the RPE cells. We look forward to investigating this promising approach in the clinic later this year.”