A team of researchers at St. Jude Children’s Research Hospital have discovered that mature eye cells called rod photoreceptor cells are better at producing retinal cells than fibroblastderived cells generated from skin. The findings could significantly advance treatments.
Led by Professor Michael Dyer, the team grew two types of stem cells in a ‘3-D culture’ and measured their ability to produce retinal cells. Stem cells are immature cells that can differentiate into more specialised cells in the body. In early clinical trials, researchers are testing whether stem cells can be differentiated into cells to replace those that are defective and die off in diseases such as age-related macular degeneration, retinitis pigmentosa and Stargardt’s disease.
Besides the 3-D culture technique, the researchers also used a set of measurements, called STEM-RET, which enabled them to quantify precisely how successful different retinal cells are in generating retinal cells. Their STEM-RET analysis revealed that the rodderived stem cells produced more retinal cells than did the fibroblast stem cells. The fibroblastderived retinal cells were missing some cell types needed for fully functional retinas.
Professor Dyer and his colleagues also explored the biological differences in the two stem cell types that could explain their differences in producing retinal cells. Specifically, the researchers analysed differences in the epigenetic control machinery of the two types. Such epigenetic machinery of cells consists of biological switches that control the cell’s genes. These are distinct from the genetic control machinery built into the DNA structure of the cell’s genes themselves.
Scientists believe that different stem cell types may retain an “epigenetic memory” – a distinctive set of epigenetic switches, even as they are reprogrammed from mature cell types. This “memory” affects how well the stem cells produce different cell types. In their analysis of the retinal cells, the researchers detected a type of epigenetic switch, called CTCF, which contributes to the epigenetic memory of the rod-derived stem cells. This epigenetic switch, they believe, could play a role in making the rod stem cells a superior source of retinal cells.
Professor Dyer said that STEM-RET scoring of stem cells represents a significant advance in determining which stem cells to use in retinal stem cell therapies.
“There has long been a debate in the field about how to standardise the quantification of stem cell differentiation,” he said. “Our STEM-RET method enables that standardisation, which means that laboratories can accurately compare their results with one another and different stem cell lines can be compared with one another. We believe the method could be adopted widely.”
Epigenetic analysis of such stem cells could lead to “epigenetic fingerprints” characterising different stem cell types. “Such fingerprints would tell researchers which stem cell lines would most likely be effective in making retinal cells, bone marrow cells or other types of mature cells for therapeutic purposes,” said Professor Dyer.
The 3-D culture technique and STEM-RET measurement protocol allow scientists to manipulate stem cells genetically and with drugs to discover ways to better reprogram the cells into functional mature cells for therapeutic use.