One approach to treating retinal diseases such as age-related macular degeneration is transplantation of the cells under the retina, i.e., the retinal pigment epithelium (RPE), but life-long immune suppression drugs are required to prevent rejection. Researchers using induced pluripotent stem cells (iPSC) have demonstrated alternatives that do not trigger rejection, but that process uses viruses to introduce the desired reprogramming factors. Currently, the U.S. FDA has not allowed clinical trials using virally generated iPSC.
A team of Medical University of South Carolina (MUSC) scientists led by Lucian V. Del Priore, M.D., Ph.D., Pierre Gautier Jenkins Professor in the Department of Ophthalmology, has demonstrated a successful alternative to viral induction--exposing skin cells to human proteins—and reported on these results in the November 25, 2015 PLOS ONE. This alternative lays the groundwork for providing a safer way to generate RPE cells for transplantation.
“This works because ultimately the DNA creates a protein inside the cell, which then affects the cell’s behavior,” explains Del Priore. The efficiency is low; only about 1% of cells become transformed, he reports, but the research established that these cells can then be turned into RPE and that these cells function normally in the Petri dish. Specifically, the work demonstrated that the generated RPE can ingest outer segments from the retina, which is important in the normal maintenance of this delicate neural tissue. Work on this project involved a collaborative research team that included Ernesto Moreira, M.D.; Jie Gong, M.D., Ph.D.; Mark Fields, Ph.D., MPH; and Zsolt Ablonczy, Ph.D.
Another team led by Del Priore reported on a "chemical peel" of the substrate under the RPE, which is damaged by retinal disease as well. Successful transplantation depends upon a healthy substrate. The investigators’ successful rejuvenation of the tissue was reported in Translational Vision Science and Technology 2015 (Oct 30;4(5):10.