Hepatology Communications,
Год журнала:
2024,
Номер
8(11)
Опубликована: Окт. 29, 2024
HCC,
the
most
common
type
of
primary
liver
cancer,
is
a
leading
cause
cancer-related
mortality
worldwide.
Although
advancement
immunotherapies
by
immune
checkpoint
inhibitors
(ICIs)
that
target
programmed
cell
death
1
or
1-ligand
has
revolutionized
treatment
for
majority
still
not
beneficial.
Accumulating
evidence
pointed
out
potent
immunosuppressive
tumor
microenvironment
in
HCC
poses
great
challenge
to
ICI
therapeutic
efficacy.
As
key
component
microenvironment,
tumor-associated
macrophages
(TAMs)
play
vital
roles
development,
progression,
and
low
responsiveness.
Mechanistically,
TAM
can
promote
cancer
invasion
metastasis,
angiogenesis,
epithelial-mesenchymal
transition,
maintenance
stemness,
importantly,
immunosuppression.
Targeting
TAMs,
therefore,
represents
an
opportunity
enhance
efficacy
patients
with
HCC.
While
previous
research
primarily
focused
on
biochemical
cues
influencing
macrophages,
emerging
highlights
critical
role
biophysical
signals,
such
as
substrate
stiffness,
topography,
external
forces.
In
this
review,
we
summarize
influence
characteristics
within
regulate
phenotype
function
TAMs
pathogenesis
progression.
We
also
explore
possible
mechanisms
discuss
potential
manipulating
regulating
therapy.
By
gaining
deeper
understanding
how
sense
respond
mechanical
forces,
may
potentially
usher
path
toward
curative
approach
combinatory
immunotherapies.
Frontiers in Immunology,
Год журнала:
2025,
Номер
15
Опубликована: Янв. 6, 2025
Inflammation
is
a
vital
immune
response,
tightly
orchestrated
through
both
biochemical
and
biophysical
cues.
Dysregulated
inflammation
contributes
to
chronic
diseases,
highlighting
the
need
for
novel
therapies
that
modulate
responses
with
minimal
side
effects.
While
several
pathways
of
are
well
understood,
influence
physical
properties
such
as
substrate
curvature
on
cell
behavior
remains
underexplored.
This
study
investigates
how
impacts
macrophage
cytoskeletal
dynamics,
gene
expression,
immunophenotype
mechanosensitive
pathways.
Gelatin-based
microgels
tunable
surface
curvatures
were
fabricated
via
water-in-oil
emulsification
crosslinked
genipin.
Microgels
sorted
into
three
size
ranges,
yielding
high
(40-50
µm),
intermediate
(150-250
low
(350-400
µm)
profiles.
Macrophages
seeded
onto
these
microgels,
dynamics
examined
using
confocal
microscopy,
SEM,
actin-specific
staining.
Gene
expression
pro-
anti-inflammatory
markers
was
quantified
qPCR.
The
role
actin
polymerization
assessed
Latrunculin-A
(Lat-A)
treatment.
adhered
effectively
high-
low-curvature
displaying
curvature-dependent
morphological
changes.
Confocal
imaging
revealed
macrophages
exhibited
significantly
higher
F-actin
density
than
those
high-curvature
microgels.
Correspondingly,
qPCR
analysis
showed
upregulation
pro-inflammatory
(e.g.,
Tnf,
Nos2)
in
conditions,
while
Arg1)
elevated
conditions.
Lat-A
treatment
reduced
modulated
patterns,
confirming
regulation
phenotype.
These
findings
demonstrate
influences
by
modulating
associated
immunophenotypic
actin-mediated
transcriptional
By
controlling
curvature,
therapeutic
biomaterials
may
direct
responses,
offering
new
avenue
treating
inflammatory
diseases.
mechanobiological
approach
presents
promising
strategy
precision
immunomodulation
regenerative
medicine.
Advanced Healthcare Materials,
Год журнала:
2025,
Номер
unknown
Опубликована: Март 5, 2025
Understanding
the
interplay
between
extracellular
matrix
(ECM)
mechanics
and
macrophage
cellular
processes
is
crucial
for
bone
regeneration.
While
ECM
stiffness
has
been
extensively
studied,
role
of
viscoelasticity
(e.g.,
stress
relaxation)
in
marrow
niche
its
effects
on
function
remain
unclear.
Here,
this
study
reveals
how
orchestrates
osteogenesis
by
modulating
metabolism
through
vasodilator-stimulated
phosphoprotein
(VASP)
/
hypoxia-inducible
factor
1
alpha
(HIF1α)
signaling.
In
rapid
maxillary
expansion
(RME)
model,
significant
relaxation
occurs
regenerated
during
initial
17
days,
coinciding
with
increased
transforming
growth
factor-beta
(TGF-β1+)
F4/80+
macrophages.
Fast
enhances
recruitment
mesenchymal
stem
cells
(MSCs)
upregulating
TGF-β1.
Using
a
hydrogel-macrophage
system
mimicking
viscoelasticity,
cranial
defect
regeneration
significantly
improved.
Moreover,
fast
shifts
from
glycolysis
to
oxidative
phosphorylation
(OXPHOS)
via
VASP/HIF1α
signaling,
facilitating
reparative
phenotype.
These
findings
elucidate
relationship
metabolism,
suggesting
new
therapeutic
avenues
mechanomedicine.
Advanced Science,
Год журнала:
2025,
Номер
unknown
Опубликована: Март 4, 2025
Macrophages
are
essential
for
immune
responses
and
maintaining
tissue
homeostasis,
exhibiting
a
wide
range
of
phenotypes
depending
on
their
microenvironment.
The
extracellular
matrix
(ECM)
is
vital
component
that
provides
structural
support
organization
to
tissues,
with
stiffness
acting
as
key
regulator
macrophage
behavior.
Using
physiologically
relevant
3D
stiffening
hydrogel
models,
it
found
increased
alone
promoted
polarization
toward
pro-regenerative
phenotype,
mimicking
the
effect
interleukin-4(IL-4)
in
softer
matrices.
Blocking
Calcium/calmodulin-dependent
kinase
2
(CaMKK2)
selectively
inhibited
stiffness-induced
without
affecting
IL-4-driven
pathways.
In
functional
studies,
CaMKK2
deletion
prevented
M2-like/pro-tumoral
caused
by
stiffening,
which
turn
hindered
tumor
growth.
murine
wound
healing
model,
loss
impaired
stiffness-mediated
accumulation,
ultimately
disrupting
vascularization.
These
findings
highlight
critical
role
mechanosensitive
fate
determination
gene
expression
program,
positioning
this
promising
therapeutic
target
modulate
pathologically
stiff
tissues.
Regenerative Biomaterials,
Год журнала:
2023,
Номер
11
Опубликована: Ноя. 10, 2023
Abstract
Dental-derived
stem
cells
(DSCs)
are
attractive
cell
sources
due
to
their
easy
access,
superior
growth
capacity
and
low
immunogenicity.
They
can
respond
multiple
extracellular
matrix
signals,
which
provide
biophysical
biochemical
cues
regulate
the
fate
of
residing
cells.
However,
direct
transplantation
DSCs
suffers
from
poor
proliferation
differentiation
toward
functional
survival
rates
local
inflammation.
Recently,
elegant
advances
in
design
novel
biomaterials
have
been
made
give
promise
use
biomimetic
various
behaviors,
including
proliferation,
migration.
Biomaterials
could
be
tailored
with
functionalities,
e.g.,
stimuli-responsiveness.
There
is
an
emerging
need
summarize
recent
engineered
biomaterials-mediated
delivery
therapy
potential
applications.
Herein,
we
outlined
for
supporting
host
response
transplantation.
Abstract
Interaction
between
tumor‐associated
macrophages
and
tumor
cells
is
crucial
for
development,
metastasis,
the
related
immune
process.
However,
are
highly
heterogeneous
spanning
from
anti‐tumorigenic
to
pro‐tumorigenic,
which
needs
be
understood
at
single‐cell
level.
Herein,
a
sessile
microdroplet
system
designed
monitoring
cellular
behavior
analyzing
intercellular
interaction,
demonstrated
with
macrophage‐tumor
cell
pairs
presented.
An
automatic
procedure
based
on
inkjet
printing
method
utilized
precise
pairing
co‐encapsulation
of
heterotypic
within
picoliter
droplets.
The
nature
microdroplets
ensures
controlled
fusion
provides
stable
environments
conducive
adherent
culture.
nitric
oxide
generation
morphological
changes
over
incubation
explored
reveal
complicated
interactions
perspective.
response
under
distinct
microenvironments
recorded.
results
demonstrate
that
microenvironment
displays
modulating
role
in
polarizing
into
pro‐tumorigenic
phenotype.
approach
versatile
compatible
platform
investigate
interaction
level,
showing
promising
potential
advancing
studies.