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

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.