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The genetically modified polysialylated form of neural cell adhesion molecule-positive cells for potential treatment of X-linked adrenoleukodystrophy.
[x-linked adrenoleukodystrophy]
Cell
transplantation
of
myelin-producing
exogenous
cells
is
being
extensively
explored
as
a
means
of
remyelinating
axons
in
X-
linked
adrenoleukodystrophy
.
We
determined
whether
3
,
3
'
,
5
-
Triiodo-
L-
thyronine
(
T
3
)
overexpresses
the
ABCD
2
gene
in
the
polysialylated
(
PSA
)
form
of
neural
cell
adhesion
molecule
(
NCAM
)
-
positive
cells
and
promotes
cell
proliferation
and
favors
oligodendrocyte
lineage
differentiation
.
P
SA-NCAM
+
cells
from
newborn
Sprague-
Dawley
rats
were
grown
for
five
days
on
uncoated
dishes
in
defined
medium
with
or
without
supplementation
of
basic
fibroblast
growth
factor
(
bFGF
)
and
/
or
T
3
.
Then
,
PSA-NCAM
+
spheres
were
prepared
in
single
cells
and
transferred
to
polyornithine
/
fibronectin-coated
glass
coverslips
for
five
days
to
determine
the
fate
of
the
cells
according
to
the
supplementation
of
these
molecules
.
T
3
responsiveness
of
ABCD
2
was
analyzed
using
real-time
quantitative
polymerase
chain
reaction
,
the
growth
and
fate
of
cells
were
determined
using
5
-
bromo-
2
-
deoxyuridine
incorporation
and
immunocytochemistry
,
respectively
.
Results
demonstrated
that
T
3
induces
overexpression
of
the
ABCD
2
gene
in
PSA-NCAM
+
cells
,
and
can
enhance
PSA-NCAM
+
cell
growth
in
the
presence
of
bFGF
,
favoring
an
oligodendrocyte
fate
.
These
results
may
provide
new
insights
into
investigation
of
PSA-NCAM
+
cells
for
therapeutic
application
to
X-
linked
adrenoleukodystrophy
.
