Affect of antidepressants on the in vitro differentiation of rat bone marrow mesenchymal stem cells into neuronal cells

Autor: Paulina Borkowska, Anna Fila-Danilow, Anna M. Bielecka, Monika Paul-Samojedny, Malgorzata Kowalczyk, Jan Kowalski, Joanna Kowalska
Rok vydání: 2015
Předmět:
Zdroj: European Journal of Pharmaceutical Sciences. 73:81-87
ISSN: 0928-0987
DOI: 10.1016/j.ejps.2015.03.016
Popis: Background Bone marrow is a valuable source of mesenchymal stem cells (MSCs) that can be used in regenerative medicine. MSCs are able to differentiate into cells from all three germ layers under specific conditions. The aim of the current work was to study the differentiation of rat MSCs (rMSCs) into neuron-like cells. New method We investigated how the antidepressants imipramine, desipramine, fluoxetine and tianeptine affect the differentiation of rMSCs. Furthermore, we present differentiation cocktails using a cortex astrocyte-conditioned medium (CACM) separately or in conjunction with each of the antidepressants and investigated their additive effect on the efficiency of differentiation. We also observed how various differentiation conditions affect the number of primary dendrites and branching dendrites per cell. Results Gene expression for an early neuronal marker ( β-III-tubulin) and markers that are typical for adult neurons such as Th , Htr2A and Slc6a4 were observed. The Tubb3 and Htr2A gene expression were up-regulated, Th decreased slightly and Slc6a4 was down-regulated after differentiation We observed a two-fold higher percentage of β-III-tubulin positive cells after treatment with antidepressants and two-fold increase of neuron-like cells after using CACM with imipramine or fluoxetine simultaneously. Differentiation using imipramine or in conjunction with CACM and desipramine or fluoxetine simultaneously increased the number of cell dendrites. Comparison with existing methods The results that were obtained are completely new and need further investigations in the nearest future. Conclusions These results suggest that antidepressants improve differentiation efficiency of rMSCs and may be useful in the preparation of rMSCs for transplantation. Differentiation efficiency is higher after long-term exposure to antidepressants, than after a 24-h exposure. Nearly additive effect of CACM and imipramine or fluoxetine suggests a beneficial role of antidepressants after transplantation.
Databáze: OpenAIRE