Publication Name	World Journal of Stem Cells
Manuscript ID	124640
DOI	10.4252/wjsc.124640
Country	China

Category	Cell & Tissue Engineering
Manuscript Type	Basic Study
Article Title	Human bone marrow-derived mesenchymal stem cells alleviate fluoxetine-resistant depression-like behaviors in mice by multi-target effects in the hippocampus
Manuscript Source	Unsolicited Manuscript
All Author List	Yu Liu, Jian-Fei Wu, Mao-Ya Xu, Ji Kang, An-Hong Ye, Bo Liu and Ke-Zhi Liu
Funding Agency and Grant Number	Funding Agency Grant Number Zigong Key Science and Technology Plan (Collaborative Innovation Project of Zigong Institute of Brain Sciences) 2025NKY0104, 2025NKY0201, 2025NKY0105 Health Commission of Zigong High-Level Talent Development Project WJW-GCCRC025 Zigong Key Science and Technology Plan (Collaborative Innovation Project of Zigong Institute of Brain Sciences) 2024-NKY-01-04 Collaborative Innovation Project of Zigong Integrated Traditional Chinese and Western Medicine Research Institute 2025ZXY0206 Health Commission of Sichuan Province Medical Science and Technology Program 25QNMP018
Corresponding Author	Bo Liu, PhD, Center for Psychiatry Research, Zigong Mental Health Center, No. 666 Gongshu Road, Gongjing District, Zigong 643020, Sichuan Province, China. liubo2511@163.com
Key Words	Major depressive disorder; Treatment-resistant depression; Chronic unpredictable restraint stress; Corticosterone; Fluoxetine; Human bone marrow-derived mesenchymal stem cells; Neuroinflammation; Neurogenesis; Brain-derived neurotrophic factor/tropomyosin receptor kinase B/cAMP response element-binding signaling
Core Tip	We established a mouse model of fluoxetine-resistant depression (FRD) by combining chronic unpredictable restraint stress with corticosterone administration. Systemic administration of human bone marrow-derived mesenchymal stem cells (hBMSCs) exerted robust antidepressant-like effects through multiple mechanisms, including suppression of hippocampal neuroinflammation, restoration of astrocytic integrity, protection of neuronal survival, and promotion of adult neurogenesis. These effects were associated with reactivation of the brain-derived neurotrophic factor/tropomyosin receptor kinase B/cAMP response element-binding signaling pathway. hBMSCs did not engraft in the brain, suggesting paracrine-mediated actions. Our findings support the use of hBMSCs as a promising multi-target therapeutic strategy for FRD, an early stage of treatment-resistant depression.
Citation	Liu Y, Wu JF, Xu MY, Kang J, Ye AH, Liu B, Liu KZ. Human bone marrow-derived mesenchymal stem cells alleviate fluoxetine-resistant depression-like behaviors in mice by multi-target effects in the hippocampus. World J Stem Cells 2026; In press DOI: https://doi.org/10.4252/wjsc.124640
PDF	124640-in-press.pdf

Received	2026-06-23 06:46
Peer-Review Started	2026-06-23 06:46
First Decision by Editorial Office Director
Return for Revision	2026-07-06 11:30
Revised	2026-07-19 09:04
Publication Fee Transferred	2026-08-02 10:54
Second Decision by Editor	2026-09-07 02:34
Second Decision by Editor-in-Chief
Final Decision by Editorial Office Director	2026-10-14 08:40
Articles in Press	2026-10-14 08:40
Edit the Manuscript by Language Editor
Typeset the Manuscript

ISSN	1948-0210 (online)
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Copyright	©Author(s) (or their employer(s)) 2026. No commercial re-use. See Permissions. Published by Baishideng Publishing Group Inc.
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