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Placental mesenchymal stem cells of fetal origin deposit epigenetic alterations during long-term culture under serum-free condition.
[severe combined immunodeficiency]
Objective
:
Fetal
placental
mesenchymal
stem
cells
(
fPMSCs
)
have
shown
promising
cell
therapy
potentials
.
However
,
their
genetic
and
epigenetic
stability
during
in
vitro
propagation
has
not
been
well
studied
.
We
thus
interrogated
the
methylation
alterations
and
tumorigenicity
of
fPMSCs
after
in
vitro
expansion
using
serum-free
medium
.
Research
design
and
methods
:
The
properties
of
fPMSCs
cultured
in
a
serum-free
medium
at
passage
3
and
passage
8
were
ascertained
by
determining
their
MSC
markers
,
proliferative
capacity
,
chromosomal
stability
,
activity
of
global
DNA
methyltransferases
and
methylation
profile
.
Their
potential
of
malignant
transformation
was
also
evaluated
in
a
severe
combined
immunodeficiency
(
SCID
)
murine
model
.
Results
:
The
fPMSCs
could
maintain
their
MSC
characteristics
but
quickly
reached
a
senescent
state
of
proliferation
during
in
vitro
expansion
.
246
genes
with
differential
DNA
methylation
of
promoters
were
identified
,
along
with
a
significantly
downregulated
global
DNA
methyltransferase
activity
.
The
genes
associated
with
aging
and
tumorigenesis
had
a
significantly
demethylated
tendency
over
in
vitro
propagation
.
However
,
the
deposition
of
epigenetic
alterations
did
not
translate
into
malignant
transformation
in
SCID
mice
.
Conclusion
:
The
fPMSCs
cultured
in
serum-free
medium
have
a
tendency
to
deposit
methylation
modifications
over
in
vitro
expansion
,
therefore
the
detection
of
genetic
and
/
or
epigenetic
alterations
is
necessary
for
fPMSCs
before
they
are
employed
for
clinical
uses
.
Diseases
Validation
Diseases presenting
"tumorigenesis had a significantly demethylated tendency over in vitro propagation"
symptom
severe combined immunodeficiency
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