Concise review: prospects of stem cell therapy for temporal lobe epilepsy.
Certain regions of the adult brain have the ability for partial self-repair after injury through production of new neurons via activation of neural stem/progenitor cells (NSCs). Nonetheless, there is no evidence yet for pervasive spontaneous replacement of dead neurons by newly formed neurons leading to functional recovery in the injured brain. Consequently, there is enormous interest for stimulating endogenous NSCs in the brain to produce new neurons or for grafting of NSCs isolated and expanded from different brain regions or embryonic stem cells into the injured brain. Temporal lobe epilepsy (TLE), characterized by hyperexcitability in the hippocampus and spontaneous seizures, is a possible clinical target for stem cell-based therapies. This is because these approaches have the potential to curb epileptogenesis and prevent chronic epilepsy development and learning and memory dysfunction after hippocampal damage related to status epilepticus or head injury. Grafting of NSCs may also be useful for restraining seizures during chronic epilepsy. The aim of this review is to evaluate current knowledge and outlook pertaining to stem cell-based therapies for TLE. The first section discusses the behavior of endogenous hippocampal NSCs in human TLE and animal models of TLE and evaluates the role of hippocampal neurogenesis in the pathophysiology and treatment of TLE. The second segment considers the prospects for preventing or suppressing seizures in TLE using exogenously applied stem cells. The final part analyzes problems that remain to be resolved before initiating clinical application of stem cell-based therapies for TLE. Disclosure of potential conflicts of interest is found at the end of this article.
Shetty
Ashok K
AK
Department of Surgery (Neurosurgery), Duke University Medical Center, Durham, North Carolina 27710, USA. Ashok.Shetty@duke.edu
Hattiangady
Bharathi
B
D000818:Animals; D001930:Brain Injuries / Q000150:complications; D016380:Brain Tissue Transplantation; D002454:Cell Differentiation; D004195:Disease Models, Animal; D018450:Disease Progression; D053595:Embryonic Stem Cells / Q000637:transplantation; D004833:Epilepsy, Temporal Lobe / Q000209:etiology / Q000473:pathology / Q000503:physiopathology / Q000601:surgery*; D006085:Graft Survival; D006624:Hippocampus / Q000473:pathology / Q000503:physiopathology; D006801:Humans; D008934:Mitogens / Q000494:pharmacology / Q000627:therapeutic use; D009474:Neurons / Q000166:cytology; D010862:Pilocarpine / Q000633:toxicity; D051381:Rats; D012598:Sclerosis; D033581:Stem Cell Transplantation; D014183:Transplantation, Heterologous
D008934:Mitogens; D010862:Pilocarpine