title: A cell-free extract from human adipose stem cells protects mice against epilepsy.
abstract: OBJECTIVE
  Stem cell-based therapies are being considered for various neurologic diseases, such as epilepsy. Recent studies have suggested that some effects of transplanted stem cells are due to bystander effects that modulate the host environment, rather than direct effects of cell replacement. The extract from human adipose stem cells (ASCs) that secrete multiple growth factors including cytokines and chemokines may be a potential source of bystander effects for the treatment of epilepsy, in which inflammation is thought to play an important role. Here, we investigated the effects of a cytosolic extract of human ASCs (ASCs-E) in a mouse model of epilepsy.
  
  
  METHODS
  Human ASCs-E, boiled ASCs-E, or fibroblast-extract (fibroblast-E) was intraperitoneally administrated to C57BL/6 mice 15 min before pilocarpine-induced status epilepticus (SE) or during chronic epileptic stage. Blood-brain barrier (BBB) leakage was evaluated by measuring Evans blue dye extravasation. Spontaneous recurrent seizure (SRS) was investigated by long-term video-electroencephalography (EEG) monitoring. The mice performed elevated plus maze, open-field, light/dark transition, and novel object recognition tasks.
  
  
  RESULTS
  Acute application of human ASCs-E before SE led to earlier attenuation of seizure spike activities after treatment with diazepam, reduction of BBB leakage, and inhibition of the development of epilepsy. Human ASCs-E treatment (for 7 days) during the chronic epileptic stage suppressed SRS and reduced abnormal epileptic behavioral phenotypes. However, neither boiled ASCs-E nor fibroblast-E had any effects in the experimental epilepsy model.
  
  
  CONCLUSIONS
  Our results demonstrate that human ASCs-E prevents or inhibits epileptogenesis and SRS in mice. They also suggest a stem cell-based, noninvasive therapy for the treatment of epilepsy.
authors.affiliation: Electrophysiological & Behavioral Brain Science Laboratory, Department of Bio and Brain Engineering, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, Korea.
authors.forename: Daejong
authors.initials: D
authors.lastname: Jeon
authors.forename: Kon
authors.initials: K
authors.lastname: Chu
authors.forename: Soon-Tae
authors.initials: ST
authors.lastname: Lee
authors.forename: Keun-Hwa
authors.initials: KH
authors.lastname: Jung
authors.forename: Kyung-Mook
authors.initials: KM
authors.lastname: Kang
authors.forename: Jae-Joon
authors.initials: JJ
authors.lastname: Ban
authors.forename: Soyun
authors.initials: S
authors.lastname: Kim
authors.forename: Jin Soo
authors.initials: JS
authors.lastname: Seo
authors.forename: Chong-Hyun
authors.initials: CH
authors.lastname: Won
authors.forename: Manho
authors.initials: M
authors.lastname: Kim
authors.forename: Sang Kun
authors.initials: SK
authors.lastname: Lee
authors.forename: Jae-Kyu
authors.initials: JK
authors.lastname: Roh
mesh_terms: D000273:Adipose Tissue / Q000737:chemistry*; D000818:Animals; D000831:Animals, Newborn; D000927:Anticonvulsants / Q000627:therapeutic use; D001812:Blood-Brain Barrier / Q000187:drug effects / Q000503:physiopathology; D002457:Cell Extracts / Q000627:therapeutic use*; D002478:Cells, Cultured; D003975:Diazepam / Q000627:therapeutic use; D004195:Disease Models, Animal; D004569:Electroencephalography; D004827:Epilepsy / Q000139:chemically induced / Q000188:drug therapy* / Q000401:mortality; D005070:Evans Blue; D005106:Exploratory Behavior / Q000187:drug effects; D005347:Fibroblasts / Q000737:chemistry; D020869:Gene Expression Profiling / Q000379:methods; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D008297:Male; D018782:Maze Learning / Q000187:drug effects / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D010862:Pilocarpine / Q000009:adverse effects; D018709:Statistics, Nonparametric; D013234:Stem Cells / Q000737:chemistry*; D013997:Time Factors
chemical_list: D000927:Anticonvulsants; D002457:Cell Extracts; D010862:Pilocarpine; D005070:Evans Blue; D003975:Diazepam