Neuronal Differentiation of Bone Marrow-derived Stromal Stem Cells Involves Suppression of Discordant Phenotypes through Gene Silencing

Tissue engineering involves the construction of transplantable tissues in which bone marrow aspirates may serve as an accessible source of autogenous multipotential mesenchymal stem cells. Increasing reports indicate that the lineage restriction of adult mesenchymal stem cells may be less establishe...

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Bibliographic Details
Published in:The Journal of biological chemistry 2005-06, Vol.280 (25), p.23691-23697
Main Authors: Egusa, Hiroshi, Schweizer, Felix E., Wang, Chia-Chien, Matsuka, Yoshizo, Nishimura, Ichiro
Format: Article
Language:English
Subjects:
Animals
Base Sequence
Bone Marrow Cells - cytology
Cell Differentiation - genetics
Cells, Cultured
DNA Primers
Gene Silencing
Hematopoietic Stem Cells - cytology
Immunohistochemistry
Mice
Multigene Family
Neurons - cytology
Oligonucleotide Array Sequence Analysis
Phenotype
Stromal Cells - cytology
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Summary:Tissue engineering involves the construction of transplantable tissues in which bone marrow aspirates may serve as an accessible source of autogenous multipotential mesenchymal stem cells. Increasing reports indicate that the lineage restriction of adult mesenchymal stem cells may be less established than previously believed, and stem cell-based therapeutics await the establishment of an efficient protocol capable of achieving a prescribed phenotype differentiation. We have investigated how adult mouse bone marrow-derived stromal cells (BMSCs) are guided to neurogenic and osteogenic phenotypes. Naïve BMSCs were found surprisingly active in expression of a wide range of mRNAs and proteins, including those normally reported in terminally differentiated neuronal cells and osteoblasts. The naïve BMSCs were found to exhibit voltage-dependent membrane currents similar to the neuronally guided BMSCs, although with smaller amplitudes. Once BMSCs were exposed to the osteogenic culture condition, the neuronal characteristics quickly disappeared. Our data suggest that the loss of discordant phenotypes during BMSC differentiation cannot be explained by the selection and elimination of unfit cells from the whole BMSC population. The percent ratio of live to dead BMSCs examined did not change during the first 8–10 days in either neurogenic or osteogenic differentiation media, and cell detachment was estimated at
ISSN:0021-9258
1083-351X
DOI:10.1074/jbc.M413796200