Researchers turn back the clock on human embryonic stem cells

Johns Hopkins scientists report success in using a cocktail of cell-signaling chemicals to further wind back the biological clock of human embryonic stem cells (ESCs), giving the cells the same flexibility researchers have prized in mice ESCs. 

The investigators say the ability to reset the stem cells' developmental clock to an earlier stage offers new opportunities to successfully coax human stem cells into making any kind of cell on demand for use as transplants and in genetic disease modeling. Eventually, they may be used to create chimeric animals from which human organs could be harvested.

Reporting on their work in the Nov. 29 Development, the researchers wrote that their so-called 3i cocktail, named for its three chemical inhibitors, produced stem cells with all the same features of classic mouse ESCs: they are easy to grow, manipulate and steer to differentiate into a variety of cell types—without the genetic instability that resulted from previous efforts to transform human stem cells.

"These cells are exactly what we've been hoping for ever since the first human ESCs were derived," says Elias Zambidis, M.D., Ph.D., associate professor of oncology at the Johns Hopkins University School of Medicine and member of the Johns Hopkins Kimmel Cancer Center and Institute for Cell Engineering.

Zambidis and his team were able to "reset" a broad range of more than 25 human stem cell lines by using this new cocktail of three chemical inhibitors. They showed that these reset human ESCs expressed genes and proteins common only in the more malleable mouse ESCs, as well as in human preimplantation embryos, but not in conventional human ESCs. They also found these newly reverted human ESCs did not have the abnormal changes in their DNA that other methods induced. The new human ESCs differentiated into transplantable vascular and neural cell types at double or triple the frequencies of conventional human ESCs.