Mesenchymal Stem Cell Therapy Modulates Peripheral-Central Immune Interactions and Attenuates...

Area of Science:

• Neuroscience
• Immunology
• Stem Cell Therapy

Background:

• Peripheral inflammation drives neuroinflammation and cognitive decline in various disorders.
• Systemic inflammation compromises blood-brain barrier integrity and activates glial cells, disrupting memory circuits.

Purpose of the Study:

• To investigate if early systemic administration of human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) can reduce inflammation-induced cognitive deficits.
• To explore the therapeutic window for MSC-based immunomodulation in chronic inflammation models.

Main Methods:

• Mice received daily lipopolysaccharide (LPS) injections for seven days to induce inflammation.
• Intravenous hUC-MSC treatment was administered immediately after LPS cessation.
• Cognitive function was assessed using behavioral tests; neuroinflammation was analyzed via cytokine and glial cell markers.

Main Results:

• LPS induced significant cognitive impairments (spatial working memory, recognition, associative learning) and neuroinflammation (microglial activation, astrocytosis, pro-inflammatory cytokine shift).
• Early hUC-MSC treatment attenuated glial reactivity and reduced pro-inflammatory cytokines while restoring IL-10 levels.
• hUC-MSC therapy partially rescued cognitive performance in the LPS-treated mice.

Conclusions:

• Early immunomodulation with hUC-MSCs can rebalance neuroimmune signaling following peripheral inflammation.
• MSC treatment limits inflammation-induced hippocampal-prefrontal circuit dysfunction and offers a potential strategy for cognitive impairment.
• This study highlights a clinically relevant therapeutic window for MSCs in inflammation-associated cognitive deficits.