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Mesenchymal stem cells increase hippocampal neurogenesis and counteract depressive-like behavior

Molecular Psychiatry volume 15, pages 1164–1175 (2010)Cite this article

Abstract

Adult bone marrow-derived mesenchymal stem cells (MSCs) are regarded as potential candidates for treatment of neurodegenerative disorders, because of their ability to promote neurogenesis. MSCs promote neurogenesis by differentiating into neural lineages as well as by expressing neurotrophic factors that enhance the survival and differentiation of neural progenitor cells. Depression has been associated with impaired neurogenesis in the hippocampus and dentate gyrus. Therefore, the aim of this study was to analyze the therapeutic potential of MSCs in the Flinders sensitive line (FSL), a rat animal model for depression. Rats received an intracerebroventricular injection of culture-expanded and 1,1′-dioctadecyl-3,3,3′,3′-tetramethylindocarbocyanine perchlorate (DiI)-labeled bone marrow-derived MSCs (105 cells). MSC-transplanted FSL rats showed significant improvement in their behavioral performance, as measured by the forced swim test and the dominant–submissive relationship (DSR) paradigm. After transplantation, MSCs migrated mainly to the ipsilateral dentate gyrus, CA1 and CA3 regions of the hippocampus, and to a lesser extent to the thalamus, hypothalamus, cortex and contralateral hippocampus. Neurogenesis was increased in the ipsilateral dentate gyrus and hippocampus of engrafted rats (granular cell layer) and was correlated with MSC engraftment and behavioral performance. We therefore postulate that MSCs may serve as a novel modality for treating depressive disorders.

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Acknowledgements

We thank Dr Albert Pinhasov, Department of Molecular Biology, Ariel University Center of Samaria for his helpful comments and Mrs Esther Furman for editing this paper.

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  1. Department of Molecular Biology, Ariel University Center of Samaria, Ariel, Israel

    M Tfilin & G Turgeman

  2. Neuropharmacology Section, the Mina and Everard Goodman Faculty of Life Sciences and the Leslie and Susan Gonda (Goldschmied) Multidisciplinary Brain Research Center, Bar-Ilan University, Ramat-Gan, Israel

    M Tfilin, E Sudai, A Merenlender, I Gispan & G Yadid

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Tfilin, M., Sudai, E., Merenlender, A. et al. Mesenchymal stem cells increase hippocampal neurogenesis and counteract depressive-like behavior. Mol Psychiatry 15, 1164–1175 (2010). https://doi.org/10.1038/mp.2009.110

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