Direct conversion from mouse fibroblasts to neurons in vitro and grafted in an epileptic model

Epilepsy is one of the most common neurological disorders. The most common way to treat epilepsy is by taking antiepileptic drugs, however, still a considerable portion of patients are still suffering from intractable epilepsy so new treatment methods are needed. Cell grafting to treat neurological diseases has been tried for decades. Yet, good cells source has been hard to find. Direct conversion of neurons from a different germ line cell type (Example: Fibroblast, mesodermal) is a new field in cell conversion research, and these so called induced neurons (iN) could be a good cell source for transplantation. It may has many advantages over other cell sources, as the neurons are not going through a stage of pluripotency but are directly converted to an adult phenotype, thus reducing the likelihood of tumor formation. The conversion time might be reduced and possibly a higher chance that the cells are directed to be the desirable type. In addition, the fibroblast is an abundant cell source with strong self-proliferation abilities, which means a large amount of neurons could be produced if the conversion ratio is high. In this study, we explore the intrinsic electrophysiological properties of the iN in vitro and graft the cells to an in vitro model of hyperexcitable epileptic tissue to investigate synaptic integration in a pathological environment. Results: Conversion ratio is estimated to be 3.2%~7.5%. The converted cells are vulnerable and could not easily adapt into the hippocampal tissue forming real connections. Further trials are needed to find ways to enhance their survival ratio in a tissue environment and increase forming connections with endogenous cells. (Less)