This approach could be adding the four pluripotency-inducing proteins to cells to jumpstart the reprogramming "machine" and then improving the efficiency with a combination of chemicals, including vitamin C. Pei is currently trying to optimize the medium in which cells are grown. Although he doubts that any other anti-oxidant will have the same effect as ascorbic acid, Pei thinks that certain growth factors could further improve the culture conditions. In fact, his group found that combining vitamin C with valproic acid, which helps induce pluripotency, can improve transformation efficiency of human fibroblasts from 1 to 6 percent.
This level of efficiency could be enough to advance studies with iPS cells. "We don't need to generate 50 percent of the cells…as long as we can reproducibly generate a sufficient number of iPS lines," Kim says, adding that a 1 percent transformation efficiency could be enough.
Eventually, researchers would have to differentiate the iPS cells into certain cell types, says Kim, who himself has differentiated the more controversial embryonic stem cells into neurons to try to treat Parkinson's disease.
But, first, several studies with these vitamin C-induced pluripotent cells should be done, Kim notes. One possible problem – vitamin C causes cells to express lower levels of p53, which is important for the repair of DNA damage. Although Pei's group did not find any chromosomal abnormalities in cells grown with vitamin C, Kim says that higher resolution analysis is needed to ensure there are no mutations.
Because of the relatively high yield of Pei's method, these analyses and other studies of iPS cells should be possible. Now researchers might be able to generate enough cells to study the mechanism of and improve the safety and efficacy of iPS cells. "It's a worldwide effort to boost efficiency and make this more practical for much wider participation from the scientific community," Pei says.
*Note (12/29/09): This sentence was edited after publication to correct the year of the first human iPS cells.