European Spine Journal,
Год журнала:
2024,
Номер
33(5), С. 1713 - 1727
Опубликована: Фев. 28, 2024
Abstract
Purpose
To
investigate
the
therapeutic
potential
of
extracellular
vesicles
(EVs)
derived
from
human
nucleus
pulposus
cells
(NPCs),
with
a
specific
emphasis
on
Tie2-enhanced
NPCs,
compared
to
EVs
bone
marrow-derived
mesenchymal
stromal
(BM-MSCs)
in
coccygeal
intervertebral
disc
degeneration
(IDD)
rat
model.
Methods
were
isolated
healthy
NPCs
cultured
under
standard
(NPC
STD
-EVs)
and
Tie2-enhancing
Tie2+
conditions.
characterized,
their
was
assessed
vitro
degenerative
terms
cell
proliferation
senescence,
or
without
10
ng/mL
interleukin
(IL)-1β.
Thereafter,
16
Sprague–Dawley
rats
underwent
annular
puncture
three
contiguous
discs
develop
IDD.
Phosphate-buffered
saline,
NPC
-EVs,
BM-MSC-derived
injected
into
injured
discs,
animals
followed
for
12
weeks
until
sacrifice.
Behavioral
tests,
radiographic
height
index
(DHI)
measurements,
evaluation
pain
biomarkers,
histological
analyses
performed
assess
outcomes
EVs.
Results
NPC-derived
exhibited
typical
exosomal
morphology
efficiently
internalized
by
enhancing
proliferation,
reducing
senescence.
In
vivo,
single
injection
preserved
DHI,
attenuated
changes,
notably
reduced
mechanical
hypersensitivity.
MSC-derived
showed
marginal
improvements
over
sham
controls
across
all
measured
outcomes.
Conclusion
Our
results
underscore
regenerative
young
EVs,
particularly
surpassing
counterparts.
These
findings
raise
questions
about
validity
MSCs
as
both
EV
sources
cellular
therapeutics
against
The
study
emphasizes
critical
influence
type,
source,
culture
conditions
EV-based
therapeutics.
Frontiers in Endocrinology,
Год журнала:
2021,
Номер
12
Опубликована: Ноя. 29, 2021
Mesenchymal
stem
cell-derived
exosomes
have
been
under
investigation
as
potential
treatments
for
a
diverse
range
of
diseases,
and
many
animal
clinical
trials
achieved
encouraging
results.
However,
it
is
well
known
that
the
biological
activity
key
to
their
therapeutic
properties;
however,
till
date,
has
not
completely
understood.
Previous
studies
provided
different
explanations
mechanisms
exosomes,
including
anti-inflammatory,
immunomodulatory,
anti-aging
mechanisms.
The
pathological
effects
oxidative
stress
often
include
organ
damage,
inflammation,
disorders
material
energy
metabolism.
evidence
gathered
from
research
involving
models
indicates
antioxidant
properties,
which
can
also
explain
anti-inflammatory
cytoprotective
effects.
In
this
study,
we
summarized
in
vivo
vitro
models,
evaluated
anti-oxidant
by
demonstrating
direct
reduction
excessive
reactive
oxygen
species
(ROS),
promotion
intracellular
defence
anti-oxidative
stress,
immunomodulation
inhibiting
excess
ROS,
alteration
mitochondrial
performance.
Exosomes
exert
properties
regulating
redox
environment
explains
variety
be
preserved
among
species.
Frontiers in Bioengineering and Biotechnology,
Год журнала:
2022,
Номер
10
Опубликована: Окт. 7, 2022
Intervertebral
disc
degeneration
(IVDD)
is
a
main
cause
of
lower
back
pain,
leading
to
psychological
and
economic
burdens
patients.
Physical
therapy
only
delays
pain
in
patients
but
cannot
eliminate
the
IVDD.
Surgery
required
when
patient
tolerate
or
has
severe
neurological
symptoms.
Although
surgical
resection
IVD
decompression
laminae
eliminates
diseased
segment,
it
damages
adjacent
normal
IVD.
There
also
risk
re-protrusion
after
removal.
Cell
played
crucial
role
development
regenerative
medicine.
transplantation
promotes
regeneration
degenerative
tissue.
However,
owing
lack
vascular
structure
IVD,
sufficient
nutrients
be
provided
for
transplanted
mesenchymal
stem
cells
(MSCs).
In
addition,
dead
release
harmful
substances
that
aggravate
Extracellular
vesicles
(EVs)
have
been
extensively
studied
as
an
emerging
therapeutic
approach.
EVs
generated
by
paracrine
MSCs
retain
potential
serve
carriers
deliver
their
contents
target
regulate
cell
activity.
Owing
double-layered
membrane
structure,
low
immunogenicity
no
immune
rejection.
Therefore,
are
considered
modality
they
limited
mass
production
loading
rates.
this
review,
advantages
introduced,
application
MSC-EVs
IVDD
discussed.
The
current
limitations
future
applications
described.
Oxidative Medicine and Cellular Longevity,
Год журнала:
2022,
Номер
2022, С. 1 - 21
Опубликована: Июнь 29, 2022
Ferroptosis,
as
an
iron-dependent
form
of
necrotic
cell
death,
has
been
reported
to
affect
activities
nucleus
pulposus
cells
(NPCs).
However,
its
role
in
the
pathogenesis
intervertebral
disc
degeneration
(IDD)
is
largely
unknown.
Notably,
our
bioinformatics
analysis
predicted
that
circ_0072464
was
downregulated
IDD
mice.
Therefore,
this
study
aimed
at
clarifying
mechanisms
extracellular
vesicle-
(EV-)
encapsulated
derived
from
bone
marrow
mesenchymal
stem
(BMSCs)
NPC
ferroptosis
IDD.
EVs
were
extracted
mouse
BMSCs
(BMSC-EVs)
and
then
cocultured
with
IL-1β-induced
NPCs,
followed
by
detection
matrix
synthesis,
proliferation,
NPCs
based
on
gain-
or
loss-of-function
experiments.
It
found
uptake
BMSC-EVs
alleviated
NRF2
downregulated,
miR-431
upregulated
Mechanistically,
competitively
bound
miR-431,
which
targeted
inhibited
expression.
BMSC-derived
carrying
promote
synthesis
proliferation
inhibiting
upregulating
NRF2.
Besides,
vivo
experiments
also
confirmed
lesions
mice
through
circ_0072464/miR-431/NRF2
axis.
Collectively,
BMSC-EV-loaded
relieve
via
upregulation
miR-431-mediated
NRF2,
therefore
providing
a
potential
therapeutic
target
against
Frontiers in Endocrinology,
Год журнала:
2022,
Номер
13
Опубликована: Окт. 20, 2022
Ferroptosis,
an
iron-dependent
form
of
programmed
cell
death
marked
by
phospholipid
peroxidation,
is
regulated
complex
cellular
metabolic
pathways
including
lipid
metabolism,
iron
balance,
redox
homeostasis,
and
mitochondrial
activity.
Initial
research
regarding
the
mechanism
ferroptosis
mainly
focused
on
solute
carrier
family
7
member
11/glutathione/glutathione
peroxidase
4
(GPX4)
signal
pathway.
Recently,
novel
mechanisms
ferroptosis,
independent
GPX4,
have
been
discovered.
Numerous
pathologies
associated
with
extensive
such
as
drug-resistant
cancers,
ischemic
organ
injuries,
neurodegenerative
diseases,
are
driven
ferroptosis.
Ferroptosis
a
new
therapeutic
target
for
intervention
IVDD.
The
role
in
modulation
intervertebral
disc
degeneration
(IVDD)
significant
topic
interest.
This
topic,
IVDD
ongoing.
Herein,
we
aim
to
review
discuss
literature
explore
relationship
between
regulatory
networks
cells
nucleus
pulposus,
annulus
fibrosus,
cartilage
endplate
provide
references
future
basic
clinical
translation
treatment.
International Journal of Nanomedicine,
Год журнала:
2022,
Номер
Volume 17, С. 6201 - 6220
Опубликована: Дек. 1, 2022
Background:
The
treatment
of
critical-size
bone
defect
is
a
great
difficulty
in
orthopedics.
Osteogenesis
and
angiogenesis
are
critical
issue
during
the
process
repair
remodeling.
Mesenchymal
stem
cells
(MSCs)-derived
exosomes
have
same
therapeutic
effect
to
MSCs-based
therapies.
human
umbilical
cord
MSCs-derived
sEVs
(hUC-MSCs-sEVs)
on
vascularized
regeneration
potential
mechanism
remains
be
investigated.
Herein,
we
aimed
explore
hUC-MSCs-sEVs
defect.
Methods:
To
investigate
osteogenesis
effects
vitro,
extracted
from
hUC-MSCs,
then
were
co-incubated
with
BMSCs
HUVECs.
We
next
investigated
angiogenesis.
fabricated
3D-printed
bioglass
scaffold
Gelma/nanoclay
hydrogel
coatings
load
(BG-gel-sEVs)
ensure
vivo
sustained
efficacy
sEVs.
Finally,
skull
model
was
used
evaluate
capacity
composited
scaffolds.
Results:
facilitated
calcium
deposition
endothelial
network
formation,
inducing
osteogenic
differentiation
by
delivering
miR-23a-3p
activate
PTEN/AKT
signaling
pathway.
Additionally,
BG-gel-sEVs
achieved
vivo.
Conclusion:
This
finding
illuminated
that
promoted
pathway,
achieving
regeneration.
Keywords:
small
extracellular
vesicles,
regeneration,
angiogenesis,
miR-23a-3p,
scaffolds
Nature Communications,
Год журнала:
2023,
Номер
14(1)
Опубликована: Июнь 30, 2023
Abstract
Minimally
invasive
biodegradable
implants
with
regeneration
have
been
a
frontier
trend
in
clinic.
Degeneration
of
nucleus
pulposus
(NP)
is
irreversible
most
spine
diseases,
and
traditional
spinal
fusion
or
discectomy
usually
injure
adjacent
segments.
Here,
an
innovative
minimally
NP
scaffold
function
inspired
by
cucumber
tendril
developed
using
shape
memory
polymer
poly(glycerol-dodecanoate)
(PGD),
whose
mechanical
property
controlled
to
the
similar
human
adjusting
synthetic
parameters.
The
chemokine
stromal
cell-derived
factor-1α
(SDF-1α)
immobilized
recruiting
autologous
stem
cells
from
peripheral
tissue,
which
has
better
ability
maintaining
disc
height,
cells,
inducing
vivo
compared
PGD
without
group
hydrogel
groups
significantly.
It
provides
way
design
biodegradation
functional
recovery,
especially
for
tissue
injury,
including
NP,
cartilage
so
on.
