Journal of Nanobiotechnology,
Год журнала:
2024,
Номер
22(1)
Опубликована: Апрель 12, 2024
Abstract
Background
Early-onset
bone
dysplasia
is
a
common
manifestation
of
hypophosphatasia
(HPP),
an
autosomal
inherited
disease
caused
by
ALPL
mutation.
ablation
induces
prototypical
premature
ageing
characteristics,
resulting
in
impaired
osteogenic
differentiation
capacity
human
marrow
mesenchymal
stem
cells
(hBMMSCs).
As
angiogenesis
tightly
coupled
with
osteogenesis,
it
also
plays
necessary
role
sustaining
homeostasis.
We
have
previously
observed
decrease
expression
marker
gene
CD31
the
metaphysis
long
Alpl
+/−
mice.
However,
regulation
has
remained
largely
unknown.
Methods
Exosomes
derived
from
Normal
and
HPP
hBMMSCs
were
isolated
identified
ultracentrifugation,
transmission
electron
microscopy,
nanoparticle
size
measurement.
The
effects
on
angiogenic
patients
assessed
immunofluorescence,
tube
formation,
wound
healing
migration
assay.
exo-ELISA
Western
Blot
used
to
evaluate
exosomes
secretion
HPP,
protein
VEGF,
PDGFBB,
Angiostatin
Endostatin
respectively.
Results
verified
that
resulted
pro-angiogenic
hBMMSCs,
accounting
for
reduced
formation
umbilical
vein
endothelial
cells,
as
quantities
proteins
composition
varied
expression.
Mechanistically,
loss
function
enhanced
ATP
release.
Additional
ATP,
turn,
led
markedly
elevated
level
receptor
P2X7,
which
consequently
promoted
secretion,
decreased
promote
angiogenesis.
Conversely,
inhibition
P2X7
increased
induction
preventing
excessive
release
anti-angiogenic
deficient-hBMMSCs.
Conclusion
ALPL–ATP
axis
regulates
ability
controlling
through
receptor.
Thus,
may
be
proved
effective
therapeutic
target
accelerating
neovascularization
ALPL–deficient
defects.
Abstract
Regeneration
is
a
complex
process
affected
by
many
elements
independent
or
combined,
including
inflammation,
proliferation,
and
tissue
remodeling.
Stem
cells
class
of
primitive
with
the
potentiality
differentiation,
regenerate
self‐replication,
multidirectional
immunomodulatory
functions.
their
cytokines
not
only
inextricably
linked
to
regeneration
ectodermal
skin
tissues,
but
also
can
be
used
for
treatment
variety
chronic
wounds.
produce
exosomes
in
paracrine
manner.
cell
play
an
important
role
regeneration,
repair,
accelerated
wound
healing,
biological
properties
which
are
similar
stem
cells,
while
safer
more
effective.
Skin
bone
tissues
critical
organs
body,
essential
sustaining
life
activities.
The
weak
repairing
ability
leads
pronounced
impact
on
quality
patients,
could
alleviated
treatment.
However,
there
obstacles
that
trough
improved
bioavailability.
This
paper
summarizes
applications
mechanisms
healing.
We
propose
new
ways
utilizing
through
different
nanoformulations,
liposomes
nanoliposomes,
polymer
micelles,
microspheres,
hydrogels,
scaffold
microneedles,
improve
use
healing
regeneration.
International Journal of Molecular Sciences,
Год журнала:
2023,
Номер
24(15), С. 12046 - 12046
Опубликована: Июль 27, 2023
Although
historically,
the
traditional
bidimensional
in
vitro
cell
system
has
been
widely
used
research,
providing
much
fundamental
information
regarding
cellular
functions
and
signaling
pathways
as
well
nuclear
activities,
simplicity
of
this
does
not
fully
reflect
heterogeneity
complexity
vivo
systems.
From
arises
need
to
use
animals
for
experimental
research
testing.
Nevertheless,
animal
experimentation
presents
various
aspects
complexity,
such
ethical
issues,
which
led
Russell
Burch
1959
formulate
3R
(Replacement,
Reduction,
Refinement)
principle,
underlying
urgent
introduce
non-animal-based
methods
research.
Considering
this,
three-dimensional
(3D)
models
emerged
scientific
community
a
bridge
between
models,
allowing
achievement
differentiation
while
avoiding
The
purpose
review
is
provide
general
overview
most
common
establish
3D
culture
discuss
their
promising
applications.
Three-dimensional
cultures
have
employed
study
both
organ
physiology
diseases;
moreover,
they
represent
valuable
tool
studying
many
cancer.
Finally,
possibility
using
drug
screening
regenerative
medicine
paves
way
development
new
therapeutic
opportunities
diseases.
Journal of Clinical Medicine,
Год журнала:
2023,
Номер
12(13), С. 4385 - 4385
Опубликована: Июнь 29, 2023
Bone
metabolism
is
regulated
by
osteoblasts,
osteoclasts,
osteocytes,
and
stem
cells.
Pathologies
such
as
osteoporosis,
osteoarthritis,
osteonecrosis,
traumatic
fractures
require
effective
treatments
that
favor
bone
formation
regeneration.
Among
these,
cell
therapy
based
on
mesenchymal
cells
(MSC)
has
been
proposed.
MSC
are
osteoprogenitors,
but
their
regenerative
activity
depends
in
part
paracrine
properties.
These
mainly
mediated
extracellular
vesicle
(EV)
secretion.
EV
modulates
processes
inflammation,
angiogenesis,
proliferation,
migration,
differentiation.
Thus,
MSC-EV
currently
an
important
tool
for
the
development
of
cell-free
therapies
medicine.
This
review
describes
current
knowledge
effects
different
phases
used
intravenous
injection,
directly
or
combination
with
types
biomaterials,
preclinical
models
diseases.
They
have
shown
great
clinical
potential
medicine
applied
to
bone.
findings
should
be
confirmed
through
standardization
protocols,
a
better
understanding
mechanisms
action,
appropriate
trials.
All
will
allow
translation
human
clinic
applications.
Abstract
Orthopedic
diseases,
such
as
osteoarthritis
and
fractures,
place
a
significant
burden
on
individuals
healthcare
systems
worldwide.
Extracellular
vesicles
(EVs),
which
are
membrane‐derived
particles,
have
emerged
novel
tool
in
the
field
of
orthopedics.
EVs
play
crucial
role
diagnosing,
regenerating,
treating
orthopedic
diseases.
In
terms
diagnosis,
serve
potential
biomarkers,
carrying
unique
donor
cell
information
circulating
effectively
bodily
fluids.
Specific
biomolecules
within
EVs,
including
proteins,
nucleic
acids,
microRNAs,
hold
promise
biological
markers
for
early
detection
monitoring
shown
promoting
bone
cartilage
regeneration.
They
can
enhance
tissue
regeneration
by
stimulating
various
stem
cells
to
proliferate,
migrate,
differentiate
into
mature
chondrocytes
osteocytes.
also
target
specific
tissues,
making
them
attractive
candidates
drug
delivery
efficiently
deliver
therapeutic
cargo,
anti‐inflammatory
agents
growth
factors,
affected
sites,
enhancing
treatment
efficacy
while
minimizing
toxicity
adverse
effects.
conclusion,
Advanced Drug Delivery Reviews,
Год журнала:
2024,
Номер
207, С. 115203 - 115203
Опубликована: Фев. 9, 2024
MSCs
are
used
for
treatment
of
inflammatory
conditions
or
regenerative
purposes.
complete
cells
and
allogenic
transplantation
is
in
principle
possible,
but
mostly
autologous
use
preferred.
In
recent
years,
it
was
discovered
that
secrete
extracellular
vesicles.
These
active
budded
off
vesicles
carry
a
cargo.
The
cargo
can
be
miRNA,
protein,
lipids
etc.
transported
through
the
body
fuse
with
target
cells.
Thereby,
they
influence
phenotype
modulate
disease.
have,
like
MSCs,
immunomodulatory
capacities.
This
review
will
focus
on
those
features
discuss
their
dual
role.
Besides
immunomodulation,
regeneration
concentrate
bone,
cartilage,
tendon,
vessels
nerves.
Current
clinical
trials
immunomodulation
started
last
five
years
highlighted
as
well.
summary,
have
great
potential
disease
modulating
entity
treatment.
Their
characteristics
need
to
taken
into
account
often
both
important
having
best
effect.
Abstract
Periodontal
disease
ranks
third
among
noncommunicable
illnesses,
behind
cancer
and
cardiovascular
disease,
is
closely
related
to
the
occurrence
progression
of
various
systemic
diseases.
However,
elucidating
processes
periodontal
promoting
bone
regeneration
remains
a
challenge.
Here,
quercetin
demonstrated
reduce
oxidative
stress
state
orofacial
mesenchymal
stem
cells
(OMSCs)
in
vitro
affect
osteogenic
growth
OMSCs
through
molecular
mechanisms
that
mediate
m6A
change
Per1.
Nevertheless,
limited
therapeutic
efficacy
medication
limitations
local
resulting
from
small,
moist,
highly
dynamic
environment
make
it
challenging
treat
tissues
with
medication.
Herein,
biosafe
injectable
hydrogel
drug‐controlled
delivery
system
constructed
as
bone‐enhancing
factory
loaded
injury
tissues.
This
drug‐carrying
made
up
nanoscale
bioglass
microspheres
light‐cured
hydrogel,
allows
effective
drug
particle
loading
cementation
moist
environment.
Furthermore,
demonstrates
ability
stimulate
differentiation
Per1‐dependent
manner,
which
ultimately
promotes
repair,
suggesting
this
has
potential
for
clinical
therapy.
Cell Death Discovery,
Год журнала:
2024,
Номер
10(1)
Опубликована: Май 2, 2024
Abstract
The
escalating
threat
of
bone-related
diseases
poses
a
significant
challenge
to
human
health.
Mesenchymal
stem
cell
(MSC)-derived
extracellular
vesicles
(MSC-EVs),
as
inherent
cell-secreted
natural
products,
have
emerged
promising
treatments
for
diseases.
Leveraging
outstanding
features
such
high
biocompatibility,
low
immunogenicity,
superior
biological
barrier
penetration,
and
extended
circulating
half-life,
MSC-EVs
serve
potent
carriers
microRNAs
(miRNAs),
long
no-code
RNAs
(lncRNAs),
other
biomolecules.
These
cargo
molecules
play
pivotal
roles
in
orchestrating
bone
metabolism
vascularity
through
diverse
mechanisms,
thereby
contributing
the
amelioration
Additionally,
engineering
modifications
enhance
bone-targeting
ability
MSC-EVs,
mitigating
systemic
side
effects
bolstering
their
clinical
translational
potential.
This
review
comprehensively
explores
mechanisms
which
regulate
disease
progression.
It
delves
into
therapeutic
potential
adept
drug
carriers,
augmented
by
engineered
modification
strategies
tailored
osteoarthritis
(OA),
rheumatoid
arthritis
(RA),
osteoporosis,
osteosarcoma.
In
conclusion,
exceptional
promise
exhibited
positions
them
an
excellent
solution
with
considerable
applications
orthopedics.
Stem
cell-derived
exosomes
exert
comparable
therapeutic
effects
to
those
of
their
parental
stem
cells
without
causing
immunogenic,
tumorigenic,
and
ethical
disadvantages.
Their
advantages
are
manifested
in
the
management
a
broad
spectrum
diseases,
dosing
versatility
exemplified
by
systemic
administration
local
delivery.
Furthermore,
activation
regulation
various
signaling
cascades
have
provided
foundation
for
claimed
curative
exosomal
therapy.
Unlike
other
relevant
reviews
focusing
on
upstream
aspects
(e.g.,
yield,
isolation,
modification),
downstream
(e.g.
phenotypic
changes,
tissue
response,
cellular
behavior)
exosome
therapy,
this
unique
review
endeavors
focus
affected
pathways.
After
meticulous
dissection
literature
from
past
five
years,
we
present
comprehensive,
up-to-date,
disease-specific,
pathway-oriented
review.
Exosomes
sourced
types
can
regulate
major
pathways
PTEN/PI3K/Akt/mTOR,
NF-κB,
TGF-β,
HIF-1α,
Wnt,
MAPK,
JAK-STAT,
Hippo,
Notch
cascades)
minor
during
treatment
numerous
diseases
encountered
orthopedic
surgery,
neurosurgery,
cardiothoracic
plastic
general
specialties.
We
provide
novel
perspective
future
research
through
bridging
gap
between
surgical
indications
when
designing
further
preclinical
studies
clinical
trials.
Applied Sciences,
Год журнала:
2024,
Номер
14(17), С. 7912 - 7912
Опубликована: Сен. 5, 2024
Recent
decades
clearly
demonstrate
the
growing
use
of
nanomaterials
in
medical
practice,
and
their
effectiveness
is
systematically
confirmed
by
consequent
scientific
research.
An
example
dentistry
endodontic
treatment,
which,
due
to
its
specificity,
one
most
demanding
procedures,
fraught
with
numerous
challenges,
such
as
difficulties
reaching
tooth
roots
ineffective
cleaning
or
insufficient
sealing
root
canals,
which
may
lead
re-infection
damage
adjacent
structures.
The
has
a
positive
impact
on
solving
these
problems,
combination
biomaterials
nanometric
technology
makes
treatment
more
effective,
precise
comfortable
for
patients,
contributes
improving
quality
dental
care.
Currently,
high
biocompatibility
can
be
used
endodontics
components
irrigation
solutions,
rinsing
canals
drug
carriers
intracanal
use.
Nanomaterials
are
also
sealants
filling
canals.
However,
latest
research
shows
that
reducing
size
materials
“nano”
scale
significantly
affects
basic
physicochemical
properties,
leads
increased
reactivity
ability
interact
at
molecular
level.
These
unique
have
contributed
medical-related
raise
concerns
provoke
discussions
about
safety
direct
contact
tissues.
Abstract
Chronic
low
back
pain
(LBP)
caused
by
intervertebral
disc
(IVD)
degradation
is
a
serious
socioeconomic
burden
that
can
cause
severe
disabilities.
Addressing
the
underlying
pathogenic
mechanisms
of
IVD
degeneration
may
inspire
novel
therapeutic
strategy
for
LBP.
Herein,
hypoxic
preconditioning
improves
both
biological
function
MSCs
in
hostile
microenvironments
and
enhances
production
small
extracellular
vesicles
(sEVs)
with
desirable
functions.
In
vitro
results
reveal
preconditional
engineering
sEVs
(HP‐sEVs)
alleviate
inflammatory
degradation,
enhance
proliferation
nucleus
pulposus
(NP)
cells,
promote
proteoglycan
synthesis
collagen
formation.
Transcriptomic
sequencing
reveales
excellent
effects
HP‐sEVs
promoting
matrix
regeneration
through
delivery
microRNA(miR)‐7‐5p,
which
further
suppresses
p65
thus
inhibition
Cxcl2
production.
Moreover,
vivo
confirm
robust
role
same
mechanism
mediated
miR‐7‐5p
delivery.
conclusion,
this
study
provides
treating
valuable
understanding
mechanism‐of‐action
associated
chronic
lower
pain.