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TISSUE-SPECIFIC STEM CELLS

Functional Neuronal Differentiation of Bone Marrow-Derived Mesenchymal Stem Cells

^aNeurosciences Précliniques, INSERM U318, Université Joseph Fourier, CHU de Grenoble, Grenoble, France;
^bCanaux Ioniques et Signalisation, INSERM E9931, Université Joseph Fourier, CEA-Grenoble, Grenoble, France;
^cImmunopathologie des Maladies Tumorales et Autoimmunes, INSERM U475, Montpellier, France

Key Words. Adult bone marrow stem cells • Transdifferentiation • Pluripotent stem cells • Neural differentiation • Multipotential differentiation • Mesenchymal stem cells

Correspondence: Philippe Tropel, Ph.D., Neurosciences Précliniques, INSERM U318, CHU Michallon, BP217, 38043 Grenoble cedex 09, France. Telephone: 33 (0) 4 76 76 56 25; Fax: 33 (0) 4 76 76 56 19; e-mail: ptropel{at}yahoo.fr

Received December 19, 2005; accepted for publication July 27, 2006.
First published online in STEM CELLS EXPRESS   August 10, 2006.



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 MSCs can be induced by chemical compounds to express markers of these lineages. In an effort to set up a mouse model of such differentiation, we addressed the neuronal potentiality of mouse MSCs (mMSCs) that we 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 (neurofilament-light, or neurofilament 70 kDa) and class III ß-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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