Human Umbilical Cord Mesenchymal Stem Cells Ameliorated Chronic Unpredictable Mild Stress-Induced Depression and Anxiety by Alleviating Neuroinflammation

J Neuroimmune Pharmacol. 2025 Apr 24;20(1):45. doi: 10.1007/s11481-025-10198-2.

ABSTRACT

Inflammation, neurotransmitters, and apoptotic neurons are crucial elements in the progression of Major Depressive Disorder (MDD). Previous studies have demonstrated that mesenchymal stem cells (MSCs) had a positive impact on neuroinflammation and neuroprotection. In this context, human umbilical cord mesenchymal stem cells (hUC-MSCs) were administered into chronic unpredictable mild stress model (CUMS) mice to evaluate their effects on inflammation, neurotransmitters, microglia, neurons activation, and neuronal apoptosis. The distribution of hUC-MSCs within the brain was detected by CM-Dil-labelled hUC-MSCs. Our results indicated that hUC-MSCs infiltrated the brains of CUMS mice to protect the integrity of the blood-brain barrier (BBB). Furthermore, hUC-MSCs inhibited microglia activation to result in decreased inflammation levels and increased neurotransmitters, ultimately alleviating neuronal damage and regulating neuronal activity. These findings suggest that hUC-MSCs can maintain the BBB integrity and reduce neuroinflammation and neuronal damage, thereby effectively alleviating depression-like and anxiety-like behavior.

PMID:40272640 | DOI:10.1007/s11481-025-10198-2