Adult hippocampus derived soluble factors induce a neuronal-like phenotype in mesenchymal stem cells.
Bone marrow-derived mesenchymal stem cells (MSCs) are not restricted in their differentiation fate to cells of the mesenchymal lineage. They acquire a neural phenotype in vitro and in vivo after transplantation in the central nervous system. Here we investigated whether soluble factors derived from different brain regions are sufficient to induce a neuronal phenotype in MSCs. We incubated bone marrow-derived MSCs in conditioned medium (CM) derived from adult hippocampus (HCM), cortex (CoCM) or cerebellum (CeCM) and analyzed the cellular morphology and the expression of neuronal and glial markers. In contrast to muscle derived conditioned medium, which served as control, conditioned medium derived from the different brain regions induced a neuronal morphology and the expression of the neuronal markers GAP-43 and neurofilaments in MSCs. Hippocampus derived conditioned medium had the strongest activity. It was independent of NGF or BDNF; and it was restricted to the neuronal differentiation fate, since no induction of the astroglial marker GFAP was observed. The work indicates that soluble factors present in the brain are sufficient to induce a neuronal phenotype in MSCs.
Rivera
Francisco J
FJ
Department of Neurology, University of Regensburg, Franz-Josef-Strauss-Allee 11, D-93053 Regensburg, Germany.
Sierralta
Walter D
WD
Minguell
Jose J
JJ
Aigner
Ludwig
L
D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D018929:Cell Culture Techniques / Q000379:methods; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology*; D048430:Cell Shape / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D002531:Cerebellum / Q000254:growth & development / Q000378:metabolism; D002540:Cerebral Cortex / Q000254:growth & development / Q000378:metabolism; D017077:Culture Media, Conditioned / Q000737:chemistry / Q000494:pharmacology; D019922:GAP-43 Protein / Q000378:metabolism; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006624:Hippocampus / Q000254:growth & development* / Q000378:metabolism*; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D020932:Nerve Growth Factor / Q000378:metabolism; D009414:Nerve Growth Factors / Q000378:metabolism*; D016900:Neurofilament Proteins / Q000378:metabolism; D009457:Neuroglia / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D010641:Phenotype; D051381:Rats; D017208:Rats, Wistar
D019208:Brain-Derived Neurotrophic Factor; D017077:Culture Media, Conditioned; D019922:GAP-43 Protein; D005904:Glial Fibrillary Acidic Protein; D009414:Nerve Growth Factors; D016900:Neurofilament Proteins; D020932:Nerve Growth Factor