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Amniotic fluid derived mesenchymal stromal cells augment fetal lung growth in a nitrofen explant model.
[congenital diaphragmatic hernia]
Recent
experimental
work
suggests
the
therapeutic
role
of
mesenchymal
stromal
cells
(
MSCs
)
during
lung
morphogenesis
.
The
purpose
of
this
study
was
to
investigate
the
potential
paracrine
effects
of
amniotic
fluid-derived
MSCs
(
AF-MSCs
)
on
fetal
lung
growth
in
a
nitrofen
explant
model
.
Pregnant
Sprague-
Dawley
dams
were
gavage
fed
nitrofen
on
gestational
day
9
.
5
(
E
9
.
5
)
.
E
14
.
5
lung
explants
were
subsequently
harvested
and
cultured
ex
vivo
for
three
days
on
filter
membranes
in
conditioned
media
from
rat
AF-MSCs
isolated
from
control
(
AF-Ctr
)
or
nitrofen-exposed
(
AF-Nitro
)
dams
.
The
lungs
were
analyzed
morphometrically
and
by
quantitative
gene
expression
.
Although
there
were
no
significant
differences
in
total
lung
surface
area
among
hypoplastic
lungs
,
there
were
significant
increases
in
terminal
budding
among
E
14
.
5
+
3
nitrofen
explants
exposed
to
AF-Ctr
compared
to
explants
exposed
to
medium
alone
(
58
.
8
±
8
.
4
vs
.
39
.
0
±
10
.
0
terminal
buds
,
respectively
;
p
<
0
.
05
)
.
In
contrast
,
lungs
cultured
in
AF-Nitro
medium
failed
to
augment
terminal
budding
.
Nitrofen
explants
exposed
to
AF-Ctr
showed
significant
upregulation
of
surfactant
protein
C
to
levels
observed
in
normal
fetal
lungs
.
A
F-MSCs
can
augment
branching
morphogenesis
and
lung
epithelial
maturation
in
a
fetal
explant
model
of
pulmonary
hypoplasia
.
Cell
therapy
using
donor-derived
AF-MSCs
may
represent
a
novel
strategy
for
the
treatment
of
fetal
congenital
diaphragmatic
hernia
.
Diseases
Validation
Diseases presenting
"pulmonary hypoplasia"
symptom
congenital diaphragmatic hernia
megacystis-microcolon-intestinal hypoperistalsis syndrome
neonatal adrenoleukodystrophy
zellweger syndrome
This symptom has already been validated