UGA Researchers Put Stem Cells Under Precise Control

Researchers at the University of Georgia have determined for the first time exactly how to control stem cells and make them develop into the precise tissue types desired.

Despite the promise associated with the therapeutic use of human stem cells, a complete understanding of the mechanisms that control the fundamental question of whether a stem cell becomes a specific cell type within the body or remains a stem cell has—until now—eluded scientists.

The study published in the March 2 edition of the journal Cell Stem Cell, explains exactly how stem cells respond to the various signals to which they are exposed within the body. The paper reconciles years of often conflicting results from the many labs working in the field, and will allow scientists now to precisely control the development of stem cells into specific types of cells.

“We can use the information from this study as an instruction book to control the behavior of stem cells,” says lead author Stephen Dalton, a professor of cellular biology at UGA. “We’ll be able to allow them to differentiate into therapeutic cell types much more efficiently and in a far more controlled manner.”

The previous paradigm held that individual signaling molecules acted alone to set off a linear chain of events that control the fate of cells. Dalton’s study, on the other hand, reveals that a complex interplay of several molecules controls the “switch” that determines whether a stem cell stays in its undifferentiated state or goes on to become a specific cell type, such as a heart, brain or pancreatic cell.

“This work addresses one of the biggest challenges in stem cell research—figuring out how to direct a stem cell toward becoming a specific cell type,” said Marion Zatz, who oversees stem cell biology grants at the National Institutes of Health. “In this paper, Dr. Dalton puts together several pieces of the puzzle and offers a model for understanding how multiple signaling pathways coordinate to steer a stem cell toward differentiating into a particular type of cell. This framework ultimately should not only advance a fundamental understanding of embryonic development, but facilitate the use of stem cells in regenerative medicine.”

 “One of the things that surprised us was how all of the pathways ‘talk’ to each other,” says Dalton. “It’s like a house of cards; everything is totally interconnected.”

Dalton and his team spent five years creating hypotheses about the how the signals controlling stem cells  function, testing those hypotheses. The process continued until the entire system was resolved.

Dalton believes the same approach can be used in the future to improve understanding of all the developmental steps occurring as the cells in an embryo divide into specific cell types.

“Hopefully, he says, "this type of approach will give us a greater understanding of cells and how they can be manipulated so that we can progress much more rapidly toward the routine use of stem cells in therapeutic settings.”