Dr. Xu’s Publication in ACS Chemical Biology
For many applications, the stem cells are actually impurities that need to be removed, because pluripotent stem cells are capable of becoming teratomas, a type of tumor. For quality control, researchers want to figure out how to ensure that the stem-cell-derived cardiac muscle or neural progenitor or pancreas cells (or whatever) are as pure as possible.
Cardiologist and stem cell expert Chunhui Xu has been continuing a line of investigation on this topic. In a recent paper in ACS Chemical Biology, her team showed that “suicide-inducing molecules” can eliminate undifferentiated stem cells from a mixture of cells. This stem-cell-derived mixture was mostly cardiac muscle cells or their progenitors, which Xu’s team wants to use for therapeutic purposes.
Other labs have used metabolic selection – depriving cells of glucose and giving them only lactate –as a selective method for eliminating stem cells from cardiac muscle cultures. This paper shows that the “selective suicide” method works for early-stage differentiation cultures, containing cardiac progenitors, while the metabolic method works only for late-stage cultures contains beating cardiomyocytes.
In the current paper, the researchers start out with a gene that converts a prodrug, 5-fluorocytosine, into a more toxic form, 5-fluorouracil. They can then selectively (by targeting the glycan SSEA-5) introduce this gene into the stem cells, not the differentiated cells. It works when there are leftover stem cells in a culture of differentiated cells, or when stem cells are spiked into differentiated cells. Xu had previously shown, in collaboration with Shuming Nie, how a spectroscopy technique can detect stray stem cells. This approach goes one step further in eliminating the stem cells, leaving a pure culture of cardiac muscle cells or cardiac progenitor cells.
The first author is postdoctoral fellow Antonio Rampoldi, PhD. The paper represents a collaboration with M.G. Finn’s lab at Georgia Tech. Xu and her lab are in the Children’s Heart Research and Outcomes Center within the Emory-Children’s-Georgia Tech Pediatric Research Alliance.
Quinn Eastman, Science Writer, Research Communications email@example.com 404-727-7829 Office