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Cell encapsulation enhances antidepressant effect of the mesenchymal stem cells and counteracts depressive-like behavior of treatment-resistant depressed rats

Molecular Psychiatry volume 25, pages 1202–1214 (2020)Cite this article

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Abstract

Despite the advances in pharmacological therapies, only the half of depressed patients respond to currently available treatment. Thus, the need for further investigation and development of effective therapies, especially those designed for treatment-resistant depression, has been sorely needed. Although antidepressant effects of mesenchymal stem cells (MSCs) have been reported, the potential benefit of this cell therapy on treatment-resistant depression is unknown. Cell encapsulation may enhance the survival rate of grafted cells, but the therapeutic effects and mechanisms mediating encapsulation of MSCs remain unexplored. Here, we showed that encapsulation enhanced the antidepressant effects of MSCs by attenuating depressive-like behavior of Wistar Kyoto (WKY) rats, which are considered as a promising animal model of treatment-resistant depression. The implantation of encapsulated MSCs (eMSCs) into the lateral ventricle counteracted depressive-like behavior and enhanced the endogenous neurogenesis in the subventricular zone (SVZ) and the dentate gyrus (DG) of the hippocampus, whereas the implantation of MSCs without encapsulation or the implantation of eMSCs into the striatum did not show such ameliorative effects. eMSCs displayed robust and stable secretion of vascular endothelial growth factor (VEGF), brain-derived neurotrophic factor, fibroblast growth factor-2, and ciliary neurotrophic factor (CNTF), and the implantation of eMSCs into the lateral ventricle activated relevant pathways associated with these growth factors. Additionally, eMSCs upregulated intrinsic expression of VEGF and CNTF and their receptors. This study suggests that the implantation of eMSCs into the lateral ventricle exerted antidepressant effects likely acting via neurogenic pathways, supporting their utility for depression treatment.

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Acknowledgements

This research was supported by grants from Scientific Research from the Ministry of Health, Labor, and Welfare of Japan (09156274 and 24592129). We thank Masako Arao, Yoshie Ukai and Keisuke Futakuchi for their technical assistance.

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Authors and Affiliations

  1. Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1, Shikata-cho, Kita-ku, Okayama-shi, Okayama, 700-8558, Japan

    Kyohei Kin, Takao Yasuhara, Masahiro Kameda, Yousuke Tomita, Michiari Umakoshi, Ken Kuwahara, Ittetsu Kin, Naoya Kidani, Jun Morimoto, Mihoko Okazaki, Tatsuya Sasaki, Naoki Tajiri & Isao Date

  2. Department of Psychology, Kibi International University Graduate School of Psychology, 8, iga-cho, takahashi-shi, Okayama, 716-8508, Japan

    Naoki Tajiri

  3. Department of Neurosurgery, University of South Florida College Medicine, 12901 Bruce B Downs Blvd, Tampa, FL, 33612, USA

    Cesario V. Borlongan

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  1. Kyohei Kin
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Kin, K., Yasuhara, T., Kameda, M. et al. Cell encapsulation enhances antidepressant effect of the mesenchymal stem cells and counteracts depressive-like behavior of treatment-resistant depressed rats. Mol Psychiatry 25, 1202–1214 (2020). https://doi.org/10.1038/s41380-018-0208-0

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