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Magnetic Resonance Tracking of Endothelial Progenitor Cells Labeled with Alkyl-Polyethylenimine 2 kDa/Superparamagnetic Iron Oxide in a Mouse Lung Carcinoma Xenograft Model.
[severe combined immunodeficiency]
AbstractThe
potential
of
using
endothelial
progenitor
cells
(
EPCs
)
in
novel
anticancer
therapy
and
the
repair
of
vascular
injury
has
been
increasingly
recognized
.
In
the
present
study
,
EPCs
were
labeled
with
N-
alkyl-polyethylenimine
2
kDa
(
PEI
2
k
)
-
stabilized
superparamagnetic
iron
oxide
(
SPIO
)
to
facilitate
magnetic
resonance
imaging
(
MRI
)
of
EPCs
in
a
mouse
lung
carcinoma
xenograft
model
.
EPCs
derived
from
human
peripheral
blood
were
labeled
with
alkyl-
PEI
2
k
/
SPIO
.
The
viability
and
activity
of
labeled
cells
were
evaluated
using
proliferation
,
migration
,
and
tubulogenesis
assays
.
Alkyl-
PEI
2
k
/
SPIO-labeled
EPCs
were
injected
intravenously
(
group
1
)
or
mixed
and
injected
together
with
A
549
cells
subcutaneously
(
group
2
)
into
groups
of
six
mice
with
severe
combined
immunodeficiency
.
The
labeling
efficiency
with
alkyl-
PEI
2
k
/
SPIO
at
7
μg
Fe
/
mL
concentration
was
approximately
100
%
.
Quantitative
analysis
of
cellular
iron
was
6
.
062
±
0
.
050
pg
/
cell
.
No
significant
effects
on
EPC
proliferation
,
migration
,
or
tubulogenesis
were
seen
after
labeling
.
Seven
-tesla
micro-
MRI
showed
the
presence
of
schistic
or
linear
hypointense
regions
at
the
tumor
margins
starting
from
days
7
to
8
after
EPC
administration
.
This
gradually
extended
into
the
inner
tumor
layers
in
group
1
.
In
group
2
,
tumor
growth
was
accompanied
by
dispersion
of
low
-signal
intensity
regions
inside
the
tumor
.
Iron
-
positive
cells
identified
by
Prussian
blue
dye
were
seen
at
the
sites
identified
using
MRI
.
Human
CD
31
-
positive
cells
and
mouse
CD
31
-
positive
cells
were
present
in
both
groups
.
Labeling
EPCs
with
alkyl-
PEI
2
k
/
SPIO
allows
noninvasive
magnetic
resonance
investigation
of
EPC
involvement
in
tumor
neovasculature
and
is
associated
with
excellent
biocompatibility
and
MRI
sensitivity
.
Diseases
Validation
Diseases presenting
"positive cells"
symptom
canavan disease
carcinoma of the gallbladder
coats disease
congenital diaphragmatic hernia
dedifferentiated liposarcoma
epidermolysis bullosa simplex
erythropoietic protoporphyria
esophageal adenocarcinoma
hodgkin lymphoma, classical
severe combined immunodeficiency
werner syndrome
x-linked adrenoleukodystrophy
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