title: Affect of antidepressants on the in vitro differentiation of rat bone marrow mesenchymal stem cells into neuronal cells.
abstract: 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.
  
  
  METHODS
  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.
  
  
  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.
authors.affiliation: Department of Medical Genetics, School of Pharmacy with the Division of Laboratory Medicine, Medical University of Silesia, Sosnowiec, Poland. Electronic address: paubor85@gmail.com.
authors.forename: Paulina
authors.initials: P
authors.lastname: Borkowska
authors.affiliation: Department of Medical Genetics, School of Pharmacy with the Division of Laboratory Medicine, Medical University of Silesia, Sosnowiec, Poland.
authors.forename: Joanna
authors.initials: J
authors.lastname: Kowalska
authors.affiliation: Department of Medical Genetics, School of Pharmacy with the Division of Laboratory Medicine, Medical University of Silesia, Sosnowiec, Poland.
authors.forename: Anna
authors.initials: A
authors.lastname: Fila-Danilow
authors.affiliation: Department of Pharmacology, School of Medicine in Katowice, Medical University of Silesia, Katowice, Poland.
authors.forename: Anna Maria
authors.initials: AM
authors.lastname: Bielecka
authors.affiliation: Department of Medical Genetics, School of Pharmacy with the Division of Laboratory Medicine, Medical University of Silesia, Sosnowiec, Poland.
authors.forename: Monika
authors.initials: M
authors.lastname: Paul-Samojedny
authors.affiliation: Department of Medical Genetics, School of Pharmacy with the Division of Laboratory Medicine, Medical University of Silesia, Sosnowiec, Poland.
authors.forename: Malgorzata
authors.initials: M
authors.lastname: Kowalczyk
authors.affiliation: Department of Medical Genetics, School of Pharmacy with the Division of Laboratory Medicine, Medical University of Silesia, Sosnowiec, Poland.
authors.forename: Jan
authors.initials: J
authors.lastname: Kowalski
mesh_terms: D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D001253:Astrocytes / Q000187:drug effects; D001854:Bone Marrow Cells / Q000187:drug effects*; D002454:Cell Differentiation / Q000187:drug effects*; D002540:Cerebral Cortex / Q000187:drug effects; D017077:Culture Media, Conditioned; D003712:Dendrites / Q000187:drug effects; D015870:Gene Expression / Q000187:drug effects; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000187:drug effects*; D009419:Nerve Tissue Proteins / Q000096:biosynthesis / Q000235:genetics; D009474:Neurons / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D000928:Antidepressive Agents; D017077:Culture Media, Conditioned; D009419:Nerve Tissue Proteins
keywords: Antidepressants; Branching neurons; Differentiation; Mesenchymal stem cells; β-III-tubulin