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

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

Research output: Contribution to journalArticlepeer-review

8 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)1202-1214
Number of pages13
JournalMolecular Psychiatry
Volume25
Issue number6
DOIs
Publication statusPublished - Jun 1 2020

ASJC Scopus subject areas

  • Molecular Biology
  • Psychiatry and Mental health
  • Cellular and Molecular Neuroscience

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