Getting pluripotent stem cells—those early stage stem cells that can make any tissue—to actually make the cell type you want can be quite tricky. I have written before that it takes a village to raise a stem cell because they respond to everything around them from the physical pressure and rigidity of their environment to any number of already present or added chemical factors. Now, a CIRM-funded team at the University of California, Los Angeles, has shown they respond to a compound made in the maturation process itself.
As stem cells mature into specific tissue their metabolism speeds up and they convert sugar to energy more efficiently. In the process they produce compounds, various so-called metabolites, and it turns out those metabolites can be part of a feedback loop that speeds the maturation process. In particular, the UCLA team looked at the metabolite alpha-ketoglutarate and when they added it to it to stem cells in the process of turning into nerve cells in a dish, the process proceeded more quickly.
Prior research had shown alpha-ketoglutarate gets involved in regulating gene activity. The Los Angeles researchers did some testing and determined that the metabolite was indeed turning off genes needed to keep the stem cells in a stem cell state and turning on genes needed to mature the cells into nerves.
“Until very recently, metabolites have been overlooked as a way to help pluripotent stem cells differentiate,” said Michael Teitell, the senior author on the study in a university press release. “This work helps to change that view.”
The research published in Cell Metabolism showed a five to 40 percent improvement in the rate that cells matured into desired tissues. These results were based on lab cultures that already had the standard factors used to grow nerve cells, but also contained added alpha-ketoglutarate to see what a little extra of the metabolite would do. While they were looking only at nerve cells in this experiment, they speculated that the same metabolite would have similar effects in lab cultures using standard factors for growing other cell types.
The team now plans to try to determine exactly which genes the metabolite regulates. Every tidbit of information on how cells mature into desired tissues, makes it more likely we will be able to efficiently make those tissues to repair and replace tissues damaged by disease for patients in need.