Effects of FGF-2 and EGF removal on the differentiationof mouse neural precursor cells

Cell therapy for neurological disorders has advanced, and neural precursor cells (NPC) may become the ideal candidates for neural transplantation in a wide range of diseases. However, additional work has to be done to determine either the ideal culture environment for NPC expansion in vitro, without...

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Main Authors: Telma T. Schwindt, Fabiana L. Motta, Barnabé Gabriela F., Massant Cristina G., Alessander O. Guimarães, Maria Elisa Calcagnotto, João B. Pesquero, Luiz E. Mello
Format: Article
Language:English
Published: Academia Brasileira de Ciências 2009-09-01
Series:Anais da Academia Brasileira de Ciências
Subjects:
Online Access:http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0001-37652009000300009
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author Telma T. Schwindt
Fabiana L. Motta
Barnabé Gabriela F.
Massant Cristina G.
Alessander O. Guimarães
Maria Elisa Calcagnotto
João B. Pesquero
Luiz E. Mello
author_facet Telma T. Schwindt
Fabiana L. Motta
Barnabé Gabriela F.
Massant Cristina G.
Alessander O. Guimarães
Maria Elisa Calcagnotto
João B. Pesquero
Luiz E. Mello
author_sort Telma T. Schwindt
collection DOAJ
description Cell therapy for neurological disorders has advanced, and neural precursor cells (NPC) may become the ideal candidates for neural transplantation in a wide range of diseases. However, additional work has to be done to determine either the ideal culture environment for NPC expansion in vitro, without altering their plasticity, or the FGF-2 and EGF mechanisms of cell signaling in neurospheres growth, survival and differentiation. In this work we evaluated mouse neurospheres cultured with and without FGF-2 and EGF containing medium and showed that those growth factors are responsible for NPC proliferation. It is also demonstrated that endogenous production of growth factors shifts from FGF-2 to IGF-1/PDGFb upon EGF and FGF-2 withdrawal. Mouse NPC cultured in suspension showed different patterns of neuronal localization (core versus shell) for both EGF and FGF-2 withdrawal and control groups. Taken together, these results show that EGF and FGF-2 removal play an important role in NPC differentiation and may contribute to a better understanding of mechanisms of NPC differentiation. Our findings suggest that depriving NPC of growth factors prior to grafting might enhance their chance to effectively integrate into the host.<br>As terapias celulares para doenças neurológicas têm avançado e células precursoras neurais (NPC) surgem como candidatas ideais para o transplante de células neurais em muitas doenças. No entanto, trabalhos adicionais devem ser feitos para determinar o ambiente de cultivo ideal para a expansão in vitro das NPC, sem alterar sua plasticidade, e os mecanismos de sinalização celular do fator de crescimento epidérmico (EGF) e fator de crescimento de fibroblasto 2 (FGF-2) no crescimento, sobrevivência e diferenciação da neuroesfera. Nesse trabalho avaliamosNPCcultivadas na presença e na ausência de FGF-2 e EGF e mostramos que esses fatores de crescimento são responsáveis pela proliferação das NPC. Também foi demonstrado que a produção endógena de fatores de crescimento alterna de FGF-2 a fator de crescimento de insulina 1 (IGF-1) e fator de crescimento derivado de plaquetas b (PDGFb) após remoção de EGF e FGF-2. NPC de camundongo cultivadas em suspensão mostraram padrões de localização neuronal distintos (centro versus borda) tanto no grupo controle como no grupo sem EGF e FGF-2. Juntos, esses resultados mostram que a remoção de EGF e FGF-2 exerce importante ação na diferenciação de NPC e possivelmente contribui para melhor compreensão dos mecanismos envolvidos na diferenciação. Nossos achados sugerem que, privando as NPC de fatores de crescimento antes do transplante, talvez aumente as chances de que as células efetivamente se integrem ao hospedeiro.
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spelling doaj.art-c62caa9951ac4dbeb25209d5026edbf22022-12-21T23:02:44ZengAcademia Brasileira de CiênciasAnais da Academia Brasileira de Ciências0001-37651678-26902009-09-0181344345210.1590/S0001-37652009000300009Effects of FGF-2 and EGF removal on the differentiationof mouse neural precursor cellsTelma T. SchwindtFabiana L. MottaBarnabé Gabriela F.Massant Cristina G.Alessander O. GuimarãesMaria Elisa CalcagnottoJoão B. PesqueroLuiz E. MelloCell therapy for neurological disorders has advanced, and neural precursor cells (NPC) may become the ideal candidates for neural transplantation in a wide range of diseases. However, additional work has to be done to determine either the ideal culture environment for NPC expansion in vitro, without altering their plasticity, or the FGF-2 and EGF mechanisms of cell signaling in neurospheres growth, survival and differentiation. In this work we evaluated mouse neurospheres cultured with and without FGF-2 and EGF containing medium and showed that those growth factors are responsible for NPC proliferation. It is also demonstrated that endogenous production of growth factors shifts from FGF-2 to IGF-1/PDGFb upon EGF and FGF-2 withdrawal. Mouse NPC cultured in suspension showed different patterns of neuronal localization (core versus shell) for both EGF and FGF-2 withdrawal and control groups. Taken together, these results show that EGF and FGF-2 removal play an important role in NPC differentiation and may contribute to a better understanding of mechanisms of NPC differentiation. Our findings suggest that depriving NPC of growth factors prior to grafting might enhance their chance to effectively integrate into the host.<br>As terapias celulares para doenças neurológicas têm avançado e células precursoras neurais (NPC) surgem como candidatas ideais para o transplante de células neurais em muitas doenças. No entanto, trabalhos adicionais devem ser feitos para determinar o ambiente de cultivo ideal para a expansão in vitro das NPC, sem alterar sua plasticidade, e os mecanismos de sinalização celular do fator de crescimento epidérmico (EGF) e fator de crescimento de fibroblasto 2 (FGF-2) no crescimento, sobrevivência e diferenciação da neuroesfera. Nesse trabalho avaliamosNPCcultivadas na presença e na ausência de FGF-2 e EGF e mostramos que esses fatores de crescimento são responsáveis pela proliferação das NPC. Também foi demonstrado que a produção endógena de fatores de crescimento alterna de FGF-2 a fator de crescimento de insulina 1 (IGF-1) e fator de crescimento derivado de plaquetas b (PDGFb) após remoção de EGF e FGF-2. NPC de camundongo cultivadas em suspensão mostraram padrões de localização neuronal distintos (centro versus borda) tanto no grupo controle como no grupo sem EGF e FGF-2. Juntos, esses resultados mostram que a remoção de EGF e FGF-2 exerce importante ação na diferenciação de NPC e possivelmente contribui para melhor compreensão dos mecanismos envolvidos na diferenciação. Nossos achados sugerem que, privando as NPC de fatores de crescimento antes do transplante, talvez aumente as chances de que as células efetivamente se integrem ao hospedeiro.http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0001-37652009000300009células precursoras neuraisneuroesferafator de crescimento de fibroblasto 2fator de crescimento epidérmicodiferenciaçãoneural precursor cellsneurospherefibroblast growth factor 2epidermal growth factordifferentiation
spellingShingle Telma T. Schwindt
Fabiana L. Motta
Barnabé Gabriela F.
Massant Cristina G.
Alessander O. Guimarães
Maria Elisa Calcagnotto
João B. Pesquero
Luiz E. Mello
Effects of FGF-2 and EGF removal on the differentiationof mouse neural precursor cells
Anais da Academia Brasileira de Ciências
células precursoras neurais
neuroesfera
fator de crescimento de fibroblasto 2
fator de crescimento epidérmico
diferenciação
neural precursor cells
neurosphere
fibroblast growth factor 2
epidermal growth factor
differentiation
title Effects of FGF-2 and EGF removal on the differentiationof mouse neural precursor cells
title_full Effects of FGF-2 and EGF removal on the differentiationof mouse neural precursor cells
title_fullStr Effects of FGF-2 and EGF removal on the differentiationof mouse neural precursor cells
title_full_unstemmed Effects of FGF-2 and EGF removal on the differentiationof mouse neural precursor cells
title_short Effects of FGF-2 and EGF removal on the differentiationof mouse neural precursor cells
title_sort effects of fgf 2 and egf removal on the differentiationof mouse neural precursor cells
topic células precursoras neurais
neuroesfera
fator de crescimento de fibroblasto 2
fator de crescimento epidérmico
diferenciação
neural precursor cells
neurosphere
fibroblast growth factor 2
epidermal growth factor
differentiation
url http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0001-37652009000300009
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