While it is possible to multiply mouse embryonic stem cells in culture, propagating stem cells that are specific to distinct tissues has proven to be a challenge. Researchers now say that they have developed a method to propagate neural stem cells derived from mouse embryonic stem (ES) cells.

In paper, recently published in PLoS Biology [Conti, L., et al.., vol. 3, issue 9, e283 (2005)] Austin Smith and colleagues at the Institute for Stem Cell Research, University of Edinburgh,UK, describe their novel method for propagating neural stem cells in a combination of epidermal growth factor (EGF) and fibroblast growth factor (FGF). The cells, they say, can proliferate without differentiation, or they can be allowed to mature into normal brain cells.

Neural stem cells are normally found in a specialized environment known as a neurosphere, which is thought to provide the necessary cellular signals to maintain populations of these undifferentiated cells. The authors were able to cultivate the brain stem cells without re-creating this complex neurosphere environment.

Neurospheres have significant limitations, the researchers say. “The stem cells maintained within neurospheres are not directly identifiable, have not been purified, and have an uncertain relationship to central nervous system precursor cells in vivo.”

To grow their stem cells, the group combined EGF and FGF, two small proteins that bind to stem cells and promote growth. “The resultant cultures constitute the first known example of tissue-specific stem cells that can be propagated without accompanying differentiation,” the study states.

Previously, scientists, including Smith’s group, had grown brain stem cells with FGF alone. These cells failed to differentiate and become mature. The stem cells derived from this new culture, however, matured into neurons and astrocytes upon removal of the growth factor combination. “We find that continuous provision of EGF is essential for the derivation and propagation of NS cells,” the authors write, “whether sourced from mouse ES cells or foetal brain.”

In the future, scientists, they say, may be able to use this technique to produce large quantities of neural stem cells that can be used to study the molecular mechanisms that define a tissue-specific stem cell and allow direct comparison with pluripotent ES cells. The cells may also have value for treating neurodegenerative diseases, including Huntington’s, Parkinson’s, and Alzheimer’s.

By Elizabeth Tolchin