Short-Term Withdrawal of Mitogens Prior to Plating Increases Neuronal Differentiation of Human Neural Precursor Cells

Short-Term Withdrawal of Mitogens Prior to Plating Increases Neuronal Differentiation of Human Neural Precursor Cells

Author Schwindt, Telma Tiemi Autor UNIFESP Google Scholar
Motta, Fabiana Louise Autor UNIFESP Google Scholar
Barnabe, Gabriela Filoso Autor UNIFESP Google Scholar
Massant, Cristina Goncalves Autor UNIFESP Google Scholar
Guimaraes, Alessander de Oliveira Autor UNIFESP Google Scholar
Calcagnotto, Maria Elisa Autor UNIFESP Google Scholar
Conceicao, Fabio Silva Google Scholar
Pesquero, Joao Bosco Autor UNIFESP Google Scholar
Rehen, Stevens Google Scholar
Mello, Luiz E. Autor UNIFESP Google Scholar
Institution Universidade Federal de São Paulo (UNIFESP)
Universidade Federal do Rio de Janeiro (UFRJ)
Abstract Background: Human neural precursor cells (hNPC) are candidates for neural transplantation in a wide range of neurological disorders. Recently, much work has been done to determine how the environment for NPC culture in vitro may alter their plasticity. Epidermal growth factor (EGF) and fibroblast growth factor-2 (FGF-2) are used to expand NPC; however, it is not clear if continuous exposure to mitogens may abrogate their subsequent differentiation. Here we evaluated if short-term removal of FGF-2 and EGF prior to plating may improve hNPC differentiation into neurons.Principal Findings: We demonstrate that culture of neurospheres in suspension for 2 weeks without EGF-FGF-2 significantly increases neuronal differentiation and neurite extension when compared to cells cultured using standard protocols. in this condition, neurons were preferentially located in the core of the neurospheres instead of the shell. Moreover, after plating, neurons presented radial rather than randomly oriented and longer processes than controls, comprised mostly by neurons with short processes. These changes were followed by alterations in the expression of genes related to cell survival.Conclusions: These results show that EGF and FGF-2 removal affects NPC fate and plasticity. Taking into account that a three dimensional structure is essential for NPC differentiation, here we evaluated, for the first time, the effects of growth factors removal in whole neurospheres rather than in plated cell culture.
Language English
Sponsor Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
Institutos do Milenio de Bioengenharia Tecidual
Grant number FAPESP: fellow
CNPq: fellow
Date 2009-02-27
Published in Plos One. San Francisco: Public Library Science, v. 4, n. 2, 10 p., 2009.
ISSN 1932-6203 (Sherpa/Romeo, impact factor)
Publisher Public Library Science
Extent 10
Access rights Open access Open Access
Type Article
Web of Science ID WOS:000265487800022

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