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First published online August 10, 2006
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2005-0636v1
24/12/2868
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Submitted on December 19, 2005
Accepted on July 27, 2006

Tissue-Specific Stem Cells

Functional neuronal differentiation of bone marrow-derived mesenchymal stem cells

Philippe Tropel 1*, Nadine Platet 1, Jean-Claude Platel 2, Danièle Noël 3, Mireille Albrieux 4, Alim-Louis Benabid 1, François Berger 1

1 Neurosciences Précliniques, INSERM U318, Université Joseph Fourier, CHU de Grenoble, Grenoble, France
2 Canaux Ioniques et Signalisation, INSERM E9931, Université Joseph Fourier, CEA-Grenoble, Grenoble, France; Department of Neurosurgery, Yale University School of Medicine, New Haven, Connecticut
3 Immunopathologie des Maladies Tumorales et Autoimmunes, INSERM U475, Montpellier, France
4 Canaux Ioniques et Signalisation, INSERM E9931, Université Joseph Fourier, CEA-Grenoble, Grenoble, France; Dynamique des Réseaux Neuronaux, INSERM U704, Université Joseph Fourier, Grenoble, France

* To whom correspondence should be addressed. E-mail: ptropel{at}yahoo.fr.


  Abstract

Recent results have shown the ability of bone marrow cells to migrate in the brain and to acquire neuronal or glial characteristics. In vitro, bone marrow-derived mesenchymal stem cells (MSCs) can be induced by chemical compounds to express markers of these lineages. In an effort to elaborate a mouse model of such differentiation, we addressed the neuronal potentiality of mouse MSCs (mMSCs) that we have recently purified. These cells expressed nestin, a specific marker of neural progenitors. Under differentiating conditions, mMSCs display a distinct neuronal shape and express neuronal markers NF-L and class III {beta}-tubulin. Moreover, differentiated mMSCs acquire neuron-like functions characterized by a cytosolic calcium rise in response to various specific neuronal activators. Finally, we further demonstrated for the first time that clonal mMSCs and their progeny are competent to differentiate along the neuronal pathway demonstrating that these bone marrow-derived stem cells share characteristics of widely multipotent stem cells unrestricted to mesenchymal differentiation pathways.




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