Reduction of Neuroinflammation in Epilepsy by Using Induced Pluripotent Stem (iPS) Cells-Derived Astrocytes

The ability to induce pluripotency in somatic cells by reprogramming factors offers new opportunities for drug discovery and cell therapy. Induced pluripotent stem cells have the potential to differentiate to various cell types, such as neural and glial cells. Astrocytes, the major glial cells of the central nervous system, play an important role in the function of the brain by regulating of extracellular ions and neurotransmitters, feeding and protection of neurons as well as modulating the activity of microglia. Microglia over-activation can be resulted in brain inflammation with subsequent susceptibility to epileptic seizures. Hypothesis: For many years, embryonic Stem cell transplantation has been examined to prevent seizure attacks in epilepsy. These studies have indicated that adult cells from patient have the ability to be transformed to embryonic stage and convert to a pluripotent stem cell by using some Transcription factors (such as Oct4, Sox2, Nanog, Rex1, Klf, c-Myc and LIN28). Accordingly, fibroblasts from an epileptic have also been reprogrammed to embryonic stage. The resulting iPS cells are isogenic to patient and are able to transform to neurons or glia in a suitable culture condition. Previous studies on ES cell therapy have focused more on neurons than astrocytes. Astrocytes, by secretion of glial cell-derived neurotrophic factor, not only regulate the different microglial activities, such as proliferation, migration and cell adhesion, but can also reduce destructive effects of microglia.
In this hypothesis, we suggest a reprogramming system for generating functional astrocyte from human pluripotent stem cell in the presence of neural growth factors. We hypothesize that these cells might reduce neuroinflammation induced by microglia and subsequent susceptibility to seizure. The reprogrammed cells could be used in cell replacement therapy of epilepsy.