Method Developed to Reprogram Human Cells to Better Mimic Embryonic Stem Cells

Australian scientists have developed a new method to reprogram human cells to better mimic embryonic stem cells, with significant implications for biomedical and therapeutic uses. Their transient-naïve-treatment (TNT) reprogramming strategy is described in a Nature paper.

In a revolutionary advance in the mid-2000s, it was discovered that the non-reproductive adult cells of the body, called somatic cells, could be artificially reprogrammed into a state that resembles embryonic stem (ES) cells, which have the capacity to then generate any cell of the body. The ability to artificially reprogram human somatic cells, such as skin cells, into these induced pluripotent stem (iPS) cells provided a way to make an essentially unlimited supply of ES-like cells, with widespread applications in disease modelling, drug screening and cell-based therapies.

“However, a persistent problem with the conventional reprograming process is that iPS cells can retain an epigenetic memory of their original somatic state, as well as other epigenetic abnormalities,” Ryan Lister, co-senior author of the paper explained. “This can create functional differences between the iPS cells and the ES cells they’re supposed to imitate, and specialized cells subsequently derived from them, which limits their use.”

According to Jose Polo, co-senior author, TNT reprogramming mimics the reset of a cell’s epigenome that happens in very early embryonic development. “This significantly reduces the differences between iPS cells and ES cells and maximizes the effectiveness of how human iPS cells can be applied,” he said.

“We predict that TNT reprogramming will establish a new benchmark for cell therapies and biomedical research, and substantially advance their progress,” Lister said.