Functional recovery and neuronal regeneration of a rat model of epilepsy by transplantation of Hes1-down regulated bone marrow stromal cells

Gamma-amino butyric acid (GABA)ergic cells play an important inhibitory role in epilepsy. Until now, there are no reports on promoting transplanted bone marrow stromal cells (BMSCs) to differentiate into GABAergic cells for treatment of epilepsy. In this study, hairy and enhancer of split 1 (Hes1)-down regulated BMSCs (H-BMSCs) were transplanted into an epileptic rat model to induce GABAergic cells differentiation to improve the function recovery and neuronal regeneration. First, Hes1 expression in isolated BMSCs was down regulated by Hes1 siRNA. Then, the H-BMSCs were labeled with 5-bromo-2′-deoxyuridine (BrdU) and transplanted into the lateral ventricle of pilocarpine-induced epileptic rats. To evaluate the therapeutic effects, behavior and electroencephalography (EEG) of the recipient rats were monitored in the following 4 weeks, followed by histological confirmation. The results showed that the rate of mortality, frequency of spontaneous recurrent seizures (SRS) and incidence of epileptiform waves presented a tendency to decrease after H-BMSCs transplantation. The histology results showed that (1) the transplanted H-BMSCs which migrated to the adjacent parahippocampal cortical areas expressed glutamate decarboxylase (GAD) 67, neuron-specific enolase (NSE) and some glial fibrillary acidic protein (GFAP), and (2) the neuronal density of corresponding cortical areas was significantly increased ( P < 0.01 VS. experimental group I or positive control group). Given these results and other advantages of BMSCs, such as easy harvest and minimal immunogenicity, transplantation of H-BMSCs could be a promising approach to improve the functional recovery and neuronal regeneration of epileptic model in the early stage.