Extracellular vesicles derived from mesenchymal stem cells alleviate depressive-like behavior in a rat model of chronic stress

IF 5.2 2区医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL Life sciences Pub Date : 2025-02-19 DOI:10.1016/j.lfs.2025.123479

Zaquer Suzana Munhoz Costa-Ferro , Rachel Santana Cunha , Erik Aranha Rossi , Erick Correia Loiola , Barbara Porto Cipriano , Júlio César Queiroz Figueiredo , Elisama Araújo da Silva , Adne Vitória Rocha de Lima , Adlas Michel de Jesus Ribeiro , Valdomiro Silveira Moitinho Junior , Corynne Stephanie Ahouefa Adanho , Carolina Kymie Vasques Nonaka , Ananssa Maíra dos Santos Silva , Kátia Nunes da Silva , Gisele Vieira Rocha , Fernanda Guarino De Felice , Pedro Antônio Schmidt do Prado-Lima , Bruno Solano de Freitas Souza

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Abstract

Depression is a prevalent chronic psychiatric disorder with a growing impact on global health. Current treatments often fail to achieve full remission, highlighting the need for alternative therapeutic strategies. Mesenchymal stem cells (MSCs) have attracted significant interest for their therapeutic potential in neuropsychiatric disorders, primarily due to their capacity to target neuroinflammation. This study aimed to investigate if extracellular vesicles derived from human umbilical MSCs (hucMSCs) promote behavioral beneficial actions in a rat model of chronic unpredictable mild stress (CUMS). We show that a single dose of hucMSCs or their derived EVs (hucMSC-EVs) via the tail vein alleviated depressive-like behavior in rats, reduced markers of neuroinflammation, reduced pro-inflammatory cytokines (IL-1β and TNF-α), and increased the number and dendritic complexity of DCX-positive cells in the dentate gyrus. Proteomic analysis of EVs revealed the presence of proteins involved in modulation of inflammatory processes and cell activation. Our study demonstrates EVs derived from hucMSCs can effectively mitigate depressive symptoms by modulating neuroinflammatory pathways and enhancing neurogenesis. These findings support further exploration of MSC-derived EVs as a novel therapeutic option for neuropsychiatric disorders.

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来源期刊

Life sciences 医学-药学

CiteScore

12.20

自引率

1.60%

发文量

841

审稿时长

6 months

期刊介绍： Life Sciences is an international journal publishing articles that emphasize the molecular, cellular, and functional basis of therapy. The journal emphasizes the understanding of mechanism that is relevant to all aspects of human disease and translation to patients. All articles are rigorously reviewed. The Journal favors publication of full-length papers where modern scientific technologies are used to explain molecular, cellular and physiological mechanisms. Articles that merely report observations are rarely accepted. Recommendations from the Declaration of Helsinki or NIH guidelines for care and use of laboratory animals must be adhered to. Articles should be written at a level accessible to readers who are non-specialists in the topic of the article themselves, but who are interested in the research. The Journal welcomes reviews on topics of wide interest to investigators in the life sciences. We particularly encourage submission of brief, focused reviews containing high-quality artwork and require the use of mechanistic summary diagrams.