Stem cells driven into selective suicide

The term “stem cell” is increasingly stretchy. Orthopedic specialists have been using it when referring to bone marrow concentrate or platelet rich plasma, which are marketed as treatments for joint pain. At Lab Land, we have an interest in pluripotent stem cells, which can differentiate into many types of tissues.

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.

 

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Quinn Eastman

Science Writer, Research Communications qeastma@emory.edu 404-727-7829 Office

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