Functional neuronal differentiation of bone marrow-derived mesenchymal stem cells.
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 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.
Tropel
Philippe
P
Neurosciences Précliniques, INSERM U318, Université Joseph Fourier, CHU de Grenoble, Grenoble, France. ptropel@yahoo.fr
Platet
Nadine
N
Platel
Jean-Claude
JC
Noël
Danièle
D
Albrieux
Mireille
M
Benabid
Alim-Louis
AL
Berger
François
F
D000818:Animals; D015415:Biomarkers; D001854:Bone Marrow Cells / Q000166:cytology*; D002118:Calcium / Q000378:metabolism; D002454:Cell Differentiation; D048430:Cell Shape / Q000187:drug effects; D002999:Clone Cells; D003600:Cytosol / Q000378:metabolism; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects; D007381:Intermediate Filament Proteins / Q000235:genetics / Q000378:metabolism; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D051379:Mice; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D064231:Nestin; D016900:Neurofilament Proteins / Q000235:genetics / Q000378:metabolism; D009474:Neurons / Q000166:cytology*; D011107:Polylysine / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D014404:Tubulin / Q000235:genetics / Q000378:metabolism
D015415:Biomarkers; D007381:Intermediate Filament Proteins; D009419:Nerve Tissue Proteins; C577485:Nes protein, mouse; D064231:Nestin; D016900:Neurofilament Proteins; D012333:RNA, Messenger; D014404:Tubulin; C044882:neurofilament protein L; D016222:Fibroblast Growth Factor 2; D011107:Polylysine; D002118:Calcium