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Transplantation of insulin-producing cells differentiated from human periosteum-derived progenitor cells ameliorate hyperglycemia in diabetic mice.
[severe combined immunodeficiency]
Periosteum-derived
progenitor
cells
(
PDPCs
)
isolated
from
the
adult
periosteum
can
differentiate
into
several
specific
cell
types
.
In
this
study
,
we
examined
the
characteristics
of
human
PDPCs
and
insulin
-producing
cells
(
IPCs
)
differentiated
from
PDPCs
and
their
ability
to
ameliorate
hyperglycemia
when
transplanted
into
streptozotocin-induced
nonobese
diabetic-
severe
combined
immunodeficiency
diabetic
mice
.
P
eriosteum-derived
progenitor
cells
were
isolated
from
patients
,
expanded
in
culture
,
and
subjected
to
a
three
-step
differentiation
protocol
to
produce
IPCs
.
The
expression
of
immunogenic
,
pluripotent
,
and
pancreatic
markers
was
examined
,
and
glucose-stimulated
insulin
release
in
vitro
was
also
assessed
.
Insulin
-producing
cells
that
differentiated
from
PDPCs
were
transplanted
under
the
kidney
capsule
of
streptozotocin-induced
diabetic
mice
,
and
glucose
levels
and
glucose
tolerance
were
measured
.
We
found
that
PDPCs
expressed
the
mesenchymal
stem
cell
markers
CD
7
3
,
CD
9
0
,
and
CD
105
and
the
pluripotent
markers
,
octamer-binding
transcription
factor
4
and
Nanog
,
but
not
sex-determining
region
Y-
box
2
or
Rex
1
.
Periosteum-derived
progenitor
cells
expressed
human
leukocyte
antigen-
ABC
but
did
not
express
human
leukocyte
antigen-
DR
or
the
costimulatory
molecules
CD
80
and
CD
86
.
Differentiated
IPCs
expressed
pancreatic
hormones
(
insulin
,
glucagon
,
somatostatin
,
and
glucose
transporter
2
)
,
hormone
processing
,
and
secretion
molecules
(
prohormone
convertase-
1
and
convertase-
2
,
Kir
6
.
2
)
,
and
pancreatic
transcription
factors
(
neurogenin
3
,
pancreatic
and
duodenal
homeobox
1
,
sex-determining
region
Y-
box
17
)
.
When
IPCs
were
stimulated
with
glucose
in
vitro
,
insulin
secretion
was
elevated
.
Transplantation
of
IPCs
under
the
kidney
capsules
of
diabetic
mice
improved
hyperglycemia
and
glucose
tolerance
.
Human
insulin
was
detected
in
the
serum
and
kidney
sections
of
mice
transplanted
with
IPCs
differentiated
from
PDPCs
.
These
results
suggest
that
IPCs
differentiated
from
PDPCs
might
be
an
alternative
source
of
β
cells
for
treating
diabetes
.
Diseases
Validation
Diseases presenting
"and glucose levels and glucose tolerance were measured"
symptom
severe combined immunodeficiency
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