Intracerebral delivery of the M2 polarizing cytokine interleukin 13 using mesenchymal stem cell implants in a model of temporal lobe epilepsy in mice

Abstract

Summary Objectives Neuroinflammation plays a critical role in the pathophysiology of mesial temporal lobe epilepsy. We aimed to evaluate whether intracerebral transplantation of interleukin 13–producing mesenchymal stem cells ( IL‐ 13 MSCs ) induces an M2 microglia/macrophage activation phenotype in the hippocampus with an epileptogenic insult, thereby providing a neuroprotective environment with reduced epileptogenesis. Methods Genetically engineered syngeneic IL‐ 13 MSCs or vehicle was injected within the hippocampus 1 week before the intrahippocampal kainic acid–induced status epilepticus ( SE ) in C57 BL /6J mice. Neuroinflammation was evaluated at disease onset as well as during the chronic epilepsy period (9 weeks). In addition, continuous video–electroencephalography (EEG) (vEEG) monitoring was obtained during the chronic epilepsy period (between 6 and 9 weeks after SE ). Results Evaluation of vEEG recordings suggested that IL ‐13 MSC grafts did not affect the severity and duration of SE or the seizure burden during the chronic epilepsy period, when compared to the vehicle treated SE mice. An M2‐activation phenotype was induced in microglia/macrophages that infiltrated the ‐ 13 MSC graft site, as evidenced by the arginase1 expression at the graft site at both the 2‐week and 9‐week time‐points. However, M2‐activated immune cells were rarely observed outside the graft site and, accordingly, the neuroinflammatory response or cell loss related to SE induction was not altered by IL‐ 13 MSC grafting. Moreover, an increase in the proportion of F4/80 + cells was observed in the IL‐ 13 MSC group compared to the controls. Significance Our data suggest that MSC ‐based IL‐ 13 delivery to induce M2 glial activation does not provide any neuroprotective or disease‐modifying effects in a mouse model of epilepsy. Moreover, use of cell grafting to deliver bioactive compounds for modulating neuroinflammation may have confounding effects in disease pathology of epilepsy due to the additional immune response generated by the grafted cells.