Creating stem cells may be the most controversial part of the process that we'd need to master in order to use them in potential therapies, but it's not the only difficult one. Maintaining populations of stem cells is also a challenge. Currently, standard protocols involve bathing the cells in a soup of growth factors, which can get quite expensive. Some lines also require what are called "feeder cells"—non-stem cells that keep them healthy and dividing. But contamination of stem cells by the feeders is one of the reasons that many of the federally-approved stem cell lines are considered unsuitable for use in humans. Simplifying stem cell maintenance would go a long way towards making the prospect of therapies more realistic.
An international research group may have taken a big step in that direction by performing a high-throughput drug screen using mouse stem cells (ESCs). They simply took a bunch of ESCs and grew them without any of the normal factors that keep the cells dividing. Normally, within a few days, cell divisions would stop. But the researchers gave each of 50,000 ESC populations a single molecule from a panel of complex organic molecules, and searched for ESCs that kept dividing. A total of 28 molecules out of the initial 50,000 looked promising, and further work narrowed the focus to a group of related molecules that share a complex five-ring structure made of carbon and nitrogen.
They called the most efficient of these SC1, and showed that the cells treated with this did maintain their stem cell fate. To find out why, the researchers linked SC1 to beads, and ran the contents of ESCs over them. To their surprise, not one, but two different proteins stuck to the beads. Anyone who follows cell signaling would recognize what they were: Ras-GAP and ERK, two proteins that play key roles letting cells know that they've received a signal from one of any number of growth factors. They were able to show that SC1 blocks the activity of both of these molecules.
The authors proposed that blocking Ras-GAP causes the cells to act as if a signal has been received, while blocking ERK tells the cell how to interpret the signal: as an instruction to keep dividing. Thus, the large, complex structure is probably related to the molecule having distinct regions that perform each of these two activities. Future work that narrows these regions down and separates them may make future molecules more efficient and easier to make and/or administer. In the end, this work may mean that stem cell research is about to get a lot easier.