# Cytoprotective and Immunomodulatory Properties of Mesenchymal Stem Cell Secretome and Its Effect on Organotypic Hippocampal Cultures in Mouse Model of Temporal Lobe Epilepsy

## TL;DR

This study explores how mesenchymal stem cell secretome protects brain tissue and reduces inflammation in a mouse model of epilepsy.

## Contribution

The study demonstrates the cytoprotective and immunomodulatory effects of MSC secretome during the latent phase of epileptogenesis.

## Key findings

- MSC secretome preserves progenitor cells and reduces NF-κB levels in hippocampal cultures.
- MSC secretome decreases LDH release and modulates IL-6 secretion in epileptic tissue.
- The secretome shows potential as a therapeutic strategy during the latent phase of epilepsy.

## Abstract

Temporal lobe epilepsy (TLE), the most common form of epilepsy, is often resistant to symptomatic treatment and characterized by persistent neuroinflammation, creating an urgent need for therapeutic strategies that can modulate early disease mechanisms. In this study, we examined the ability of the human MSC-derived secretome to influence epileptic hippocampal tissue during the latent phase of epileptogenesis using an ex vivo model. For this purpose, we characterized the MSC-derived secretome using multiplex Luminex profiling, optimized organotypic hippocampal cultures (OHCs) by evaluating cell viability, validated the pilocarpine-induced TLE model both morphologically and electrophysiologically, and investigated the influence of MSC-conditioned medium (MSC-CM) on epileptic hippocampal tissue. Using mouse-derived OHCs, we found that MSC-CM supports the preservation of nestin- and doublecortin (DCX)-positive progenitor cells, reduces NF-κB (p50/p105) levels, decreases LDH release into the culture medium, and modulates IL-6 secretion during the latent phase of epileptogenesis. Taken together, these findings suggest that the MSC-derived secretome exerts cytoprotective and context-dependent immunomodulatory effects, attenuating inflammatory signaling and cellular stress while supporting the preservation of neural progenitor markers in epileptic tissue. These properties highlight a potential phase-specific therapeutic window to modulate pathological processes during the latent phase of epileptogenesis.