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. Author manuscript; available in PMC: 2017 Mar 1.
Published in final edited form as: Neurosci Biobehav Rev. 2015 Dec 31;62:35–47. doi: 10.1016/j.neubiorev.2015.12.014

Table 3.

Studies on Stem Cell Grafts Generating GABA-ergic Cells in Epilepsy Models

Animal Prototype
and Type of Donor
Cells		 Timing and Site of
Grafting		 Time-point of
Seizure
Analyses
& Effects on
Seizures		 Effects on
Memory and
Mood Function		 Graft Cell Survival
Differentiation and
Integration		 Effects of
Grafts on Host
Brain Changes
Kainate induced rat
model of chronic
temporal lobe
epilepsy (TLE)
Neural stem cells
(NSCs) expanded
from E14 rat medial
ganglionic eminence
(MGE)
Waldau et al., 2010 		9–12 months after
the induction of
status epilepticus
(SE) - Rats
exhibiting
continuing
spontaneous
recurrent seizures
(SRS) and learning
and memory
dysfunction
Grafts placed into
the hippocampus		 1–3 months post-
grafting
Reduced the
frequency &
duration of SRS
by 43–51%,
Stage-V seizures
by 90%, and the
total time spent in
seizures by 74%		 No positive
effects of grafts
on spatial
learning and
memory function		 Recovery: 28% of
injected cells
Differentiation of graft-
derived cells: 10% into
gamma-amino butyric
acid positive (GABA-
ergic) neurons; 57%
into S-100β+
astrocytes; and 3% into
oligodendrocyte
progenitors. 50% of
graft-derived astrocytes
also expressed glial
cell-line derived
neurotrophic factor
(GDNF)		 Grafting restored
GDNF in host
astrocytes
Grafting did not
enhance
neurogenesis in
the hippocampus
Rat models of
kindling and
pilocarpine induced
TLE
NSCs from the
human
telencephalon of
aborted 13 weeks
gestation fetus
Lee et al., 2014 		After full kindling or
3-weeks after SE
(i.e. after the
occurrence of SRS)		 2 weeks to 3
months post-
grafting
NSC grafting
reduced: (i)
durations of
behavioral
seizures and after
discharges, and
seizure stage in
the kindling
model;
(ii) Frequency of
SRS and time
spent in seizure
activity in the
pilocarpine model		 No positive
effects of grafts
on spatial
learning and
memory function		 Recovery: 57–29% of
injected cells at 4–8
weeks post-grafting in
the kindling model;
Percentage survival not
reported for pilocarpine
model
Differentiation of graft-
derived cells: 24% into
GABA-ergic neurons;
28% into S- APC-CC1+
oligodendrocytes; and
8% into astrocytes.
50% of graft-derived
astrocytes also
expressed GDNF		 Grafting restored
the expression of
GDNF in host
astrocytes
Grafting did not
ameliorate the
aberrant mossy
fiber sprouting
Pilocarpine induced
SE in mice
Mouse embryonic
stem cell (mESC)
derived neural
progenitor cells
(NPCs) with ventral
forebrain identities
Maisano et al., 2012 		Two-weeks after
SE
Grafts were placed
into the DG		 Not examined Not examined Graft-derived GABA+
neurons displayed
electrical properties of
hilar interneurons and
received excitatory
synaptic connections		 No significant
effect on
aberrant mossy
fiber sprouting
Pilocarpine model of
SE in NOD-SCID
mice
MGE-like progenitors
from hESCs
Cunningham et al., 2014 		~3 weeks after SE
Grafts were placed
into the
hippocampus		 3 months after
grafting
93% reduction in
the frequency of
seizures; 56% of
grafted animals
displayed no
seizures (based
on continuous
EEG for 5–10
days)		 Alleviation of
hyperactivity and
aggressive
behavior;
Reversal of
short-term
working memory
and object
recognition
memory
dysfunction		 Survival: ~19% of
injected cells.
Majority of graft-
derived cells expressed
GABA and displayed
presynaptic machinery
for releasing GABA,
properties for inhibiting
host hippocampal
neurons and
postsynaptic machinery
for receiving excitatory
inputs from host
hippocampal neurons		 No effect on
aberrant mossy
fiber sprouting