Open AccessMedial Ganglionic Eminence Cells Freshly Obtained or Expanded as Neurospheres Show Distinct Cellular and Molecular Properties in Reducing Epileptic Seizures
Author(s) -
Romariz Simone A. A.,
Paiva Daisyléa S.,
Galindo Layla T.,
Barnabé Gabriela F.,
Guedes Vivian A.,
Borlongan Cesario V.,
Longo Beatriz M.
Publication year - 2017
Publication title -
cns neuroscience and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.403
H-Index - 69
eISSN - 1755-5949
pISSN - 1755-5930
DOI - 10.1111/cns.12650
Subject(s) - ganglionic eminence , neurosphere , biology , retinoic acid , microbiology and biotechnology , transplantation , progenitor cell , cell culture , stem cell , cellular differentiation , medicine , genetics , adult stem cell , gene
Summary Aims 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. Conclusion 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.