Epigenetic modifiers promote efficient generation of neural-like cells from bone marrow-derived mesenchymal cells grown in neural environment.
Understanding mechanisms that govern cell fate decisions will lead to developing techniques for induction of adult stem cell differentiation to desired cell outcomes and, thus, production of an autologos source of cells for regenerative medicine. Recently, we demonstrated that stem cells derived from adult central nervous system or bone marrow grown with other cell lineages or with more undifferentiated cells sometimes take on those characteristics. This indicates that manipulating extracellular factors may be sufficient to alter some developmental restrictions regulated by the epigenetic system. In this study, using pharmacological agents that interfere with the main components of the epigenetic program such as DNA methylation and histone deacetylation, we induce high-level expression of embryonic and neural stem cell (NSC) marker Sox2 in bone marrow-derived mesenchymal stem cells (MSCs). Exposure of these modified cells to a neural environment via juxtacrine and paracrine interactions promote efficient generation of neural stem-like cells as well as cells with neuronal and glial characteristics. We concluded that the manipulation strategy used in this study can be a useful method for efficient production of NSC-like cells from MSCs.
Alexanian
Arshak R
AR
Department of Neurosurgery, Neuroscience Research Labs, Medical College of Wisconsin, VAMC, 5000 W. National Ave 151, Milwaukee, Wisconsin 53295, USA. aalexan@mcw.edu
D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology* / Q000378:metabolism; D002454:Cell Differentiation; D049109:Cell Proliferation; D048430:Cell Shape; D002478:Cells, Cultured; D017077:Culture Media, Conditioned; D004268:DNA-Binding Proteins / Q000378:metabolism; D044127:Epigenesis, Genetic; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000378:metabolism; D051379:Mice; D009474:Neurons / Q000166:cytology* / Q000378:metabolism; D055748:SOXB1 Transcription Factors; D015534:Trans-Activators / Q000378:metabolism
D017077:Culture Media, Conditioned; D004268:DNA-Binding Proteins; D055748:SOXB1 Transcription Factors; C527783:Sox2 protein, mouse; D015534:Trans-Activators