A “fountain of youth” that sustains the production of new neurons in the brains of rodents may also be present in the human brain, researchers at Duke University Medical Center have found.

The existence of a vital support system of cells around stem cells in the brain explains why stem cells by themselves can’t generate neurons in a lab dish, a major roadblock in using these stem cells for injury repair.

The scientists found that neighboring “epithelial-like” ependymal cells — not stem cells themselves — maintain a special structure that keeps neural stem cells “neurogenic,” able to make new neurons. Currently, when neural stem cells are harvested for growth in culture, however, the ependymal cells are not removed along with them, and this can be a problem.

“Neural stem cells in a lab dish don’t continue to make neurons as they do inside the brain,” said Chay Kuo, MD, PhD, George Brumley Jr. Assistant Professor of Cell Biology, Pediatrics, and Neurobiology. “Instead, they often produce astrocytes, a cell type that may not be helpful to re-implant into a brain.” He said that uncontrolled astrocyte growth can lead to brain tumors.

They discovered that the Foxj1 transcription factor, a class of master proteins that turn other genes on and/or off, is critical to instruct ependymal cells to change shape and assemble into pinwheel-like architecture surrounding stem cells. The researchers said the lateral membranes of mature ependymal cells are shaped like machine cogs or fingers that lace together.

Kuo decided to study these cells because the lateral ventricles in the brain, where adult neural stem cells reside, are also the last area of a developing brain that grows ependymal cells. “The common radial glial progenitors in the developing nervous system prior to birth give rise to both the ependymal cells and the adult stem cells,” Kuo said. “So it made sense to study these niche cells as well as the stem cells.”

The researchers also determined that the structural protein Ankyrin 3 was turned on by Foxj1 in these ependymal cells to provide structural support for the delicate neural stem cells. Signals generated by this structural support will probably be important for instructing introduced neural stem cells to make neurons in therapeutic settings, the researchers said.

Ref.: Chay T. Kuo, et al., Ank3-Dependent SVZ Niche Assembly Is Required for the Continued Production of New Neurons, Neuron, 2011; 71 (1): 61-75 [DOI: 10.1016/j.neuron.2011.05.029]