title: Medial Ganglionic Eminence Cells Freshly Obtained or Expanded as Neurospheres Show Distinct Cellular and Molecular Properties in Reducing Epileptic Seizures.
abstract: OBJECTIVE
  Medial ganglionic eminence (MGE) progenitors give rise to inhibitory interneurons and may serve as an alternative cell source for large-scale cell transplantation for epilepsy after in vitro expansion. We investigated whether modifications in the culture medium of MGE neurospheres affect neuronal differentiation and expression of MGE-specific genes. In vivo, we compared anticonvulsant effects and cell differentiation pattern among neurospheres grown in different culture media and compared them with freshly harvested MGE cells.
  
  
  METHODS
  We used four variations of cell culture: standard, containing growth factors (EGF/FGF-2) (GF); addition of retinoic acid (GF-RA); withdrawal of EGF/FGF-2 (WD); and addition of retinoic acid and withdrawal of EGF/FGF-2 (WD-RA). Based on in vitro results neurosphere-grown (WD-RA or GF conditions) or fresh MGE cells were transplanted into the hippocampus.
  
  
  RESULTS
  In vitro WD-RA showed increased neuronal population and higher expression of Dlx1, Nkx2.1, and Lhx6 genes in comparison with GF culture condition. After transplantation, fresh MGE cells and neurospheres (GF) showed anticonvulsant effects. However, fresh MGE cells differentiated preferentially into inhibitory neurons, while GF gave rise to glial cells.
  
  
  CONCLUSIONS
  We conclude that freshly isolated and neurosphere-grown MGE cells reduced seizures by different mechanisms (inhibitory interneurons vs. astrocytes). Fresh MGE cells appear more appropriate for cell therapies targeting inhibitory interneurons for conferring anticonvulsant outcomes.
authors: Departamento de Fisiologia, Universidade Federal de São Paulo-UNIFESP, São Paulo, SP, Brazil.
authors: Simone A A
authors: SA
authors: Romariz
authors: Departamento de Fisiologia, Universidade Federal de São Paulo-UNIFESP, São Paulo, SP, Brazil.
authors: Daisyléa S
authors: DS
authors: Paiva
authors: Departamento de Bioquímica, Universidade Federal de São Paulo-UNIFESP, São Paulo, SP, Brazil.
authors: Layla T
authors: LT
authors: Galindo
authors: Ludwig Institute for Cancer Research at Instituto Sírio-Libanês de Ensino e Pesquisa, São Paulo, SP, Brazil.
authors: Gabriela F
authors: GF
authors: Barnabé
authors: Department of Neurosurgery and Brain Repair, University of South Florida, Tampa, FL, USA.
authors: Vivian A
authors: VA
authors: Guedes
authors: Department of Neurosurgery and Brain Repair, University of South Florida, Tampa, FL, USA.
authors: Cesario V
authors: CV
authors: Borlongan
authors: Departamento de Fisiologia, Universidade Federal de São Paulo-UNIFESP, São Paulo, SP, Brazil.
authors: Beatriz M
authors: BM
authors: Longo
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D003401:Creatine / Q000378:metabolism; D004195:Disease Models, Animal; D004622:Embryo, Mammalian; D004815:Epidermal Growth Factor / Q000494:pharmacology; D004827:Epilepsy / Q000139:chemically induced / Q000378:metabolism* / Q000601:surgery*; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D060850:LIM-Homeodomain Proteins / Q000378:metabolism; D008473:Median Eminence / Q000166:cytology*; D018721:Muscarinic Agonists / Q000633:toxicity; D009474:Neurons / Q000187:drug effects / Q000637:transplantation*; D009478:Neuropeptide Y / Q000378:metabolism; D010320:Parvalbumins / Q000378:metabolism; D010751:Phosphopyruvate Hydratase / Q000378:metabolism; D010862:Pilocarpine / Q000633:toxicity; D051381:Rats; D017207:Rats, Sprague-Dawley; D014212:Tretinoin / Q000494:pharmacology
chemical_list: D005904:Glial Fibrillary Acidic Protein; D060850:LIM-Homeodomain Proteins; D018721:Muscarinic Agonists; D009478:Neuropeptide Y; D010320:Parvalbumins; D010862:Pilocarpine; D016222:Fibroblast Growth Factor 2; D014212:Tretinoin; D004815:Epidermal Growth Factor; D010751:Phosphopyruvate Hydratase; D003401:Creatine
keywords: Epilepsy; Interneuronal progenitors; Medial ganglionic eminence; Neurospheres; Transplantation