Purification of immature neuronal cells from neural stem cell progeny

Azari, Hassan, Osborne, Geoffrey W., Yasuda, Takahiro, Golmohammadi, Mohammed G., Rahman, Maryam, Deleyroll, Loic P., Esfandiari, Ebrahim, Adams, David J., Scheffler, Bjorn, Steindler, Dennis A. and Reynolds, Brent A. (2011) Purification of immature neuronal cells from neural stem cell progeny. PLoS One, 6 6: e20941. doi:10.1371/journal.pone.0020941

Author Azari, Hassan
Osborne, Geoffrey W.
Yasuda, Takahiro
Golmohammadi, Mohammed G.
Rahman, Maryam
Deleyroll, Loic P.
Esfandiari, Ebrahim
Adams, David J.
Scheffler, Bjorn
Steindler, Dennis A.
Reynolds, Brent A.
Title Purification of immature neuronal cells from neural stem cell progeny
Journal name PLoS One   Check publisher's open access policy
ISSN 1932-6203
Publication date 2011-06-03
Sub-type Article (original research)
DOI 10.1371/journal.pone.0020941
Open Access Status DOI
Volume 6
Issue 6
Start page e20941
Total pages 16
Editor Fabrizio Gelain
Place of publication United States
Publisher Public Library of Science
Collection year 2012
Language eng
Abstract 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.
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Queensland Brain Institute Publications
Official 2012 Collection
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Citation counts: TR Web of Science Citation Count  Cited 17 times in Thomson Reuters Web of Science Article | Citations
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Created: Wed, 31 Aug 2011, 11:49:46 EST by Debra McMurtrie on behalf of Queensland Brain Institute