TY - JOUR T1 - Purification of Immature Neuronal Cells from Neural Stem Cell Progeny A1 - Azari, Hassan A1 - Osborne, Geoffrey W. A1 - Yasuda, Takahiro A1 - Golmohammadi, Mohammad G. A1 - Rahman, Maryam A1 - Deleyrolle, Loic P. A1 - Esfandiari, Ebrahim A1 - Adams, David J. A1 - Scheffler, Bjorn A1 - Steindler, Dennis A. A1 - Reynolds, Brent A. Y1 - 2011/06/03 N2 - Large-scale proliferation and multi-lineage differentiation capabilities make neural stem cells (NSCs) a promising renewable source of cells for therapeutic applications. However, the practical application for neuronal cell replacement is limited by heterogeneity of NSC progeny, relatively low yield of neurons, predominance of astrocytes, poor survival of donor cells following transplantation and the potential for uncontrolled proliferation of precursor cells. To address these impediments, we have developed a method for the generation of highly enriched immature neurons from murine NSC progeny. Adaptation of the standard differentiation procedure in concert with flow cytometry selection, using scattered light and positive fluorescent light selection based on cell surface antibody binding, provided a near pure (97%) immature neuron population. Using the purified neurons, we screened a panel of growth factors and found that bone morphogenetic protein-4 (BMP-4) demonstrated a strong survival effect on the cells in vitro, and enhanced their functional maturity. This effect was maintained following transplantation into the adult mouse striatum where we observed a 2-fold increase in the survival of the implanted cells and a 3-fold increase in NeuN expression. Additionally, based on the neural-colony forming cell assay (N-CFCA), we noted a 64 fold reduction of the bona fide NSC frequency in neuronal cell population and that implanted donor cells showed no signs of excessive or uncontrolled proliferation. The ability to provide defined neural cell populations from renewable sources such as NSC may find application for cell replacement therapies in the central nervous system. JF - PLOS ONE JA - PLOS ONE VL - 6 IS - 6 UR - https://doi.org/10.1371/journal.pone.0020941 SP - e20941 EP - PB - Public Library of Science M3 - doi:10.1371/journal.pone.0020941 ER -