image: Differentiation of human iPSC-MGE cells (red) into neuropeptide Y positive interneurons (green) in the epileptic hippocampus. view more
Credit: Image courtesy of Ashok K. Shetty.
A study explores a potential treatment for chronic epilepsy. Status epilepticus (SE), a prolonged period of seizures without recovery, can lead to chronic epilepsy. Grafting of medial ganglionic eminence (MGE) cells into the hippocampus following SE has been explored as a potential treatment for chronic epilepsy, but the long-term efficacy and clinical potential of such grafts have not been established. Darwin Prockop, Ashok Shetty, and colleagues generated human MGE-like cells from human induced pluripotent stem cells (hiPSC) and transplanted the cells into the hippocampus of rats following SE induction. In the chronic epileptic phase after SE, over a 3-week period, rats that received MGE grafts had a lower frequency of spontaneous recurrent seizures and spent less time in seizure activity than rats that did not receive grafts. MGE grafts also alleviated SE-induced cognitive and mood dysfunctions observed in control rats. Rats with grafts exhibited reductions in abnormal neurogenesis, interneuron loss, and aberrant mossy fiber sprouting, compared with control rats. Pharmacologic inactivation of graft-derived interneurons led to an increase in seizure activity. The results support the therapeutic efficacy of hiPSC-derived MGE cells for alleviating chronic epilepsy and raise the possibility of autologous MGE grafts. Autologous grafts could preclude the need for immune suppression after grafting and promote long-term graft-host integration, according to the authors.
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Article #18-14185: "Human induced pluripotent stem cell-derived MGE cell grafting after status epilepticus attenuates chronic epilepsy and comorbidities via synaptic integration," by Dinesh Upadhya et al.
MEDIA CONTACT: Ashok K. Shetty, Texas A&M Health Science Center College of Medicine, College Station, TX; tel: 979-436-9653, 919-518-5265; e-mail: shetty@medicine.tamhsc.edu
Journal
Proceedings of the National Academy of Sciences