"People have studied this mechanism for 10 to 20 years," said Ding. "It is a fundamental mechanism."
Ding and colleagues tested a number of drug-like molecules, looking for those that inhibited the TGFb (transforming growth factor beta) and the MEK (mitogen-activated protein kinase) pathways, which are known to be involved in the MET process. The researchers identified the most active compounds, then looked at their effects on stem cell creation when used singly and in combination.
The researchers found two chemicals ALK5 inhibitor SB43142 and MEK inhibitor PD0325901 used in combination were highly effective in promoting the transformation of fibroblasts into stem cells.
"This method is the first in human cells that is mechanism-specific for the reprogramming process," said Ding.
And the two-chemical technique bested the efficiency of the classic genetic method by 100 times.
Efficient, Fast, Safe
But the researchers thought they might be able to do even better.
Attempting to increase the efficiency of the process even further, the team decided to enlist another natural pathway, the cell survival pathway. After screening a library of compounds targeting this pathway, the team focused on a novel compound called Thiazovivin.
The researchers found that a technique using Thiazovivin in combination with the two previously selected chemicals, SB43142 and PD0325901, beat the efficiency of the classic method by 200 times.
In addition, while the classic method required four weeks to complete, the new method took two weeks.
In addition to its virtues of speed and efficiency, Ding emphasizes that the safety profile of the new method is highly promising. Not only is the method based on natural biologica
|Contact: Keith McKeown|
Scripps Research Institute