DUARTE, Calif., December 13, 2009 — City of Hope researchers identified the mechanism through which neural stem cells can continue growing and multiplying without differentiating from their stem cell state. The work by the institution’s Department of Neurosciences, reported Dec. 13 in the online edition of Nature Cell Biology, establishes a firm foundation for the development of safe stem cell therapies.
“One of the biggest challenges to stem cell therapies is simply having enough stem cells,” said Yanhong Shi, Ph.D., assistant professor of neurosciences and senior author on the study. “We need to know how to expand them in order to apply them to therapies”.
Until now, scientists were not sure what signaled neural stem cells — stem cells that eventually can become nerve and brain cells — to simply renew themselves and grow without differentiating. Shi and her team believe they have found the controlling signal.
Stem cells’ healing potential to cure a multitude of diseases ranging from cancer and diabetes to spinal cord injury and neurodegenerative diseases, such as Alzheimer’s and Parkinson’s diseases, arises from their ability to differentiate and become many different cell types in the body, such as nerve, muscle and blood cells. However, the body also must maintain a continuous supply of self-renewing stem cells in order to supply these new differentiated cells.
In previous work, Shi and her team found that a protein called TLX was essential to keeping neural stem cells growing in the self-renewal phase. In the current research, the team discovered that TLX activates an important molecular pathway called the Wnt/β-catenin pathway.
“Wnt proteins have been shown to control the self-renewal of several types of stem cells, including blood-forming stem cells and skin stem cells,” said Shi. The current study is the first to connect TLX and Wnt proteins in self-renewing neural stem cells.
The discovery that TLX-Wnt/β-catenin pathway stimulates neural stem cell growth and self-renewal suggests ways for researchers to manipulate neural stem cells to keep them growing and renewing themselves without differentiating. Controlling this decision point is important for researchers; it will allow them to grow vast numbers of self-renewing, undifferentiated stem cells that are young and ripe for treating disease.
According to Shi, knowing the signals and molecular pathways that keep stem cells self-renewing is crucial to developing a large enough supply of stem cells to treat patients, and the current work marks a major step toward that goal.
Collaborators include scientists from Howard Hughes Medical Institute and the Salk Institute. The Whitehall Foundation, the Margaret E. Early Medical Trust and the National Institute of Neurological Disorders and Stroke supported the work.
