Soon after the exciting discovery of a method to turn human adult cells into stem cells in 2007 came the frustration of actually trying to make that transformation efficient. In creating induced pluripotent stem (iPS) cells, scientists typically only get 0.01 percent of a sample of human fibroblast (skin) cells to change.
A group led by Duanqing Pei of the Guangzhou Institutes of Biomedicine and Health in China has found that a simple chemical can boost the efficiency by 100-fold—namely, vitamin C.
The researchers can trigger the conversion to iPS cells by introducing genes or proteins to adult cells, typically with a virus. Once the cells become pluripotent, they have the ability to become any cell in the body, thereby offering the promise of repairing damaged organs and treating disease. But scientists have yet to come up with the ideal recipe. “It’s a worldwide effort to boost efficiency and make this more practical for much wider participation from the scientific community,” Pei says.
In their effort, Pei and his group started with the realization that the factors that induce cells to become pluripotent were causing the cells to make the free radicals known as reactive oxygen species (ROS). “A high level of ROS is definitely very bad for the fibroblasts,” Pei notes, because it speeds cell death. To fight off the ROS, Pei’s team tested a variety of antioxidant chemicals in the cells’ growing medium. Experimenting with mouse cells, the group found that the petri dish containing vitamin C had 30 percent more mouse cells than the dish that did not, suggesting that the antioxidant helped to ward off the effects of aging.
Surprisingly, vitamin C not only helped cells survive, but it also enhanced their progression to pluripotency. After 14 days, when cells start to become fully pluripotent, 10 to 20 percent of the mouse cells that were grown with vitamin C expressed genes associated with pluripotency, compared with only 0.1 to 0.2 percent of the colonies grown without vitamin C. The group saw a similar improvement in human fibroblast reprogramming, in which ascorbic acid boosted the conversion rate from 0.01 to 1 percent.
The researchers, who published their findings in the December 24 Cell Stem Cell, also tested other antioxidants, but none boosted the development of pluripotency the way vitamin C did. That has lead Pei to believe that, in addition to ascorbic acid’s antioxidant property, an as yet unknown mechanism plays a role. And although more detailed analysis is needed, having vitamin C around does not seem to introduce negative cellular changes.
“Overall, I think this is quite impressive progress,” remarks Kwang-Soo Kim, director of the Molecular Neurobiology Lab at Harvard Medical School. Although 1 percent may not seem all that efficient, it could be enough to push the field significantly. “We don’t need to generate 50 percent of the cells,” Kim says, “as long as we can reproducibly generate a sufficient number of iPS lines.”