An influence of trichostatin a on neuronal differentiation of human bone marrow stromal cells

Abstract

During the last years it has been shown that bone marrow stromal cells, which were earlier designated as mesenchymal stem cells [MSC], can differentiate at nonorthodoxal way in particular into cells which have endodermal or ectodermal origin. Thus, the possibility of induction of neuronal phenotype by growth factors and chemical agents has been revealed. However many questions concerning neuronal differentiation of MSC remain controversial. First of all it is conformity of differentiated stromal cells to nerve cells, since the mechanism of the differentiation remain unclear. Here we had attempt to reveal nuerogenic effects of retinoic acid [PA], a native embryonic morphogen, on MSC by histone acetylation. We used two protocols of combined treatment MSC with RA and trichostatin A [TSA], a specific inhibitor ofhistone deacetylase. In the one case the cells treated with RA and TSA regulatory. According to other protocol TSA was added to culture medium only once with first treatment MSC with RA. In the both ways of induction we observed at day 13 a transformation of 50-70% fibroblastoid stromal cells into cells with neuron-like morphology, although RA and TSA alone did not have differentiating effects. Immunofluorescent study of neuron-like differentiated cells revealed an enhancement of immunoreactivity to neuron-specific markers including NF-M and τ-1. Therefore TSA induced RA-dependent neuronal differentiation of MSC. Morphological and phenotypical changes can reflect a neurogenic influence of RA on stromal cells.

Keywords

mesenchymal stem cells / neuronal differentiation / trichostatin A / retinoic acid

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