Induction of neuron-specific enolase promoter and neuronal markers in differentiated mouse bone marrow stromal cells |
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Authors: | Yossef S Levy Doron Merims Hanna Panet Yael Barhum Eldad Melamed Daniel Offen |
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Institution: | (1) Laboratory for Neurosciences, Felsenstein Medical Research Center, Israel;(2) the Department of Neurology, Rabin Medical Center-Beilinson Campus, Petach Tikva, The Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel |
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Abstract: | Mesenchymal stem cells in the adult bone marrow are differentiated to connective tissue, muscle, bone, cartilage, and fat
cells. Recent studies in cultures, animal models, and humans demonstrated the plasticity of these cells and their capacity
to express neuronal markers. However, questions were raised as to whether the neuronal phenotypes reflect transient changes
or even fusion with neurons. In this study, we induced the differentiation of mouse stromal cells to neuron-like cells and
observed the activation of the tissue-specific promoter of neuron-specific enolase (NSE). We used transgenic (Tg) mice that
carry the antiapoptotic human bcl-2 gene, expressed only in neurons under the NSE promoter. Some previous studies have indicated that the transgene induces neuroprotection
in various animal models of neurodegenerative diseases. We found that following induction, the mouse stromal cells demonstrate
neuronal phenotype and express the neuronal marker, NeuN (neural nuclei protein). However, most of the stromal cells derived
from the Tg mice, but not the wild type, also expressed human Bcl-2, as indicated by immunocytochemistry. Furthermore, these
induced neuron-like cells were more resistant to cell death induced by dopamine. In conclusion, our experimental models showed
that stromal cells might be induced to neuronal phenotypes and activate neuronal-specific promoters. Moreover, neurons targeted
over expression of the human bcl-2 gene and provided high resistance against such apoptotic insults. This novel strategy reveals a new horizon in the improvement
of gene therapy, based on stem cell transplantation in neurodegenerative diseases. |
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Keywords: | Bone marrow stromal cells Bcl-2 neuronal plasticity neuron-specific enolase promoter |
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