Study the Therapeutic Role of Mesenchymal Stem Cells in a Model of Temporal Lobe Epilepsy

Abstract

Temporal lobe epilepsy (TLE) is one of the main refractory types of focal epilepsy characterized by unsatisfactory treatment options making it critical to search for alternative therapeutic approaches. Stem cells have been recognized as one of the potential therapeutic candidates in various diseases, following numerous investigations in animal experiments and clinical trials. This study intended to explore the influence of mesenchymal stem cells (MSCs) derived from rat bone marrow (BM-MSCs) or rat adipose tissue (AD-MSCs) on the biochemical, molecular and histopathological variations implicated in epileptogenesis of pilocarpine acute and chronic epileptic rat models. MSCs were successfully isolated, grown, propagated and recognized through morphological shape and cell surface markers gene expression. In this study, one hundred and thirty-fife adult male Wistar rats were allocated into nine groups (15 rats/group) as follow: (1) placebo group, (2) acute epileptic group, (3) acute epileptic group treated with BM-MSCs, (4) acute epileptic group treated with AD-MSCs, (5) acute epileptic group treated with carbamazepine (CBZ), (6) chronic epileptic group, (7) chronic epileptic group treated with BM-MSCs, (8) chronic epileptic group treated with AD-MSCs and (9) chronic epileptic group treated with CBZ. Homing of the infused MSCs to the injured brain tissues was confirmed by labeling them with PKH26 dye. Brain HSP-70, S100β, caspase-8, GABA, Sema4D and galanin concentrations were assayed by ELISA. Moreover, hippocampal TLR-4 and Syn-I gene expression levels were investigated by sqRT-PCR. Histological examination of hippocampal and cortical tissues were also carried out. The present data proved the morphological spindle shape and gene expression levels of the specific surface markers of the isolated MSCs. Also, the current findings demonstrated the accommodation of MSCs into the injured brain areas of acute and chronic epileptic groups. BM-MSCs or AD-MSCs infusion or CBZ administration elicited significant decline in brain HSP-70, S100β, caspase-8 levels and hippocampal TLR-4 mRNA level. Moreover, these medications constructed significant enhancement in brain GABA, galanin and Sema4D levels as well as hippocampal synapsin-I mRNA level. Ultimately, histological assessment indicated that BM-MSCs or AD-MSCs transplantation evokes refinement in the histological organization of the investigated brain areas. The outcomes of this research reveal the crucial role of MSCs in neural repair via their anti-oxidant, anti-inflammatory and anti-apoptotic properties. Also, the neuroprotective activity of MSCs has been evidenced by modulating epileptic neuronal circuit, secreting neurotrophic molecules and restoring synaptic plasticity. Thus, the present attempt provides critical insights into the mechanism of MSCs therapy in temporal lobe epilepsy in order to facilitate the development of cell-based therapy in epileptic patients.