bioRxiv (Cold Spring Harbor Laboratory),
Journal Year:
2023,
Volume and Issue:
unknown
Published: Aug. 14, 2023
Abstract
Ectopic
bone
marrow
adipocytes
(BMAds)
accumulation
occurring
under
diverse
pathophysiological
conditions
leads
to
deterioration.
Estrogen-related
receptor
α
(ESRRA)
is
a
key
regulator
responding
metabolic
stress.
Here,
we
show
that
adipocyte-specific
ESRRA
deficiency
rescues
osteogenesis
and
vascular
formation
in
adipocyte-rich
due
estrogen
or
obesity.
Mechanistically,
adipocyte
interferes
with
E2/ESR1
signaling
resulting
transcriptional
repression
of
secreted
phosphoprotein
1
(
Spp1
);
positively
modulates
Leptin
expression
by
binding
its
promoter.
abrogation
results
enhanced
SPP1
decreased
LEPTIN
secretion
from
both
visceral
BMAds,
concertedly
dictating
stromal
stem
cell
fate
commitment
restoring
type
H
vessel
formation,
constituting
feed-forward
loop
for
formation.
Pharmacological
inhibition
protects
obese
mice
against
loss
high
adiposity.
Thus,
our
findings
highlight
therapeutic
approach
via
targeting
preserve
especially
detrimental
milieu.
Graphic
abstract
Nature Communications,
Journal Year:
2025,
Volume and Issue:
16(1)
Published: Jan. 20, 2025
Abstract
Reconstructing
large,
inflammatory
maxillofacial
defects
using
stem
cell-based
therapy
faces
challenges
from
adverse
microenvironments,
including
high
levels
of
reactive
oxygen
species
(ROS),
inadequate
oxygen,
and
intensive
inflammation.
Here,
inspired
by
the
reaction
mechanisms
intracellular
antioxidant
defense
systems,
we
propose
de
novo
design
an
artificial
antioxidase
Ru-doped
layered
double
hydroxide
(Ru-hydroxide)
for
efficient
redox
homeostasis
bone
regeneration.
Our
studies
demonstrate
that
Ru-hydroxide
consists
hydroxyls-synergistic
monoatomic
Ru
centers,
which
efficiently
react
with
collaborate
hydroxyls
rapid
proton
electron
transfer,
thus
exhibiting
efficient,
broad-spectrum,
robust
ROS
scavenging
performance.
Moreover,
can
effectively
sustain
cell
viability
osteogenic
differentiation
in
elevated
environments,
modulating
microenvironment
during
tissue
regeneration
male
mice.
We
believe
this
development
offers
a
promising
avenue
designing
antioxidase-like
materials
to
treat
various
inflammation-associated
disorders,
arthritis,
diabetic
wounds,
enteritis,
fractures.
Advanced Healthcare Materials,
Journal Year:
2025,
Volume and Issue:
unknown
Published: Feb. 2, 2025
With
the
global
population
aging,
awareness
of
oral
health
is
rising.
Periodontitis,
a
widespread
bacterial
infectious
disease,
gaining
attention.
Current
novel
biomaterials
address
key
clinical
issues
like
infection,
gum
inflammation,
tooth
loosening,
and
loss,
focusing
on
antibacterial,
anti-inflammatory,
tissue
regeneration
properties.
However,
strategies
that
integrate
advantages
these
to
achieve
synergistic
therapeutic
effects
by
clearing
biofilms,
inhibiting
inflammation
activation,
restoring
periodontal
soft
hard
functions
remain
very
limited.
Recent
studies
highlight
link
between
periodontitis
systemic
diseases,
underscoring
complexity
disease.
There
an
urgent
need
find
comprehensive
treatment
plans
requirements.
Whether
integrating
new
enhance
existing
treatments
or
developing
approaches
replace
traditional
therapies,
efforts
will
drive
advancements
in
treatment.
Therefore,
this
review
compares
with
treatments.
It
highlights
design
concepts
mechanisms
functional
materials,
their
properties,
discusses
importance
strategies.
This
aims
provide
guidance
for
emerging
research
promote
development
precise
efficient
Cells,
Journal Year:
2023,
Volume and Issue:
12(16), P. 2039 - 2039
Published: Aug. 10, 2023
Mesenchymal
stromal
cells
nowadays
emerge
as
a
major
player
in
the
field
of
regenerative
medicine
and
translational
research.
They
constitute,
with
their
derived
products,
most
frequently
used
cell
type
different
therapies.
However,
heterogeneity,
including
subpopulations,
anatomic
source
isolation,
high
donor-to-donor
variability,
constitutes
controversial
issue
that
affects
use
clinical
applications.
Furthermore,
intrinsic
extrinsic
molecular
mechanisms
underlying
self-renewal
fate
specification
are
still
not
completely
elucidated.
This
review
dissects
heterogeneity
aspects
tissue
associated
distinct
developmental
origin
need
to
be
considered
when
generating
homogenous
products
before
usage
for
Nature Communications,
Journal Year:
2024,
Volume and Issue:
15(1)
Published: May 4, 2024
Abstract
Excessive
bone
marrow
adipocytes
(BMAds)
accumulation
often
occurs
under
diverse
pathophysiological
conditions
associated
with
deterioration.
Estrogen-related
receptor
α
(ESRRA)
is
a
key
regulator
responding
to
metabolic
stress.
Here,
we
show
that
adipocyte-specific
ESRRA
deficiency
preserves
osteogenesis
and
vascular
formation
in
adipocyte-rich
upon
estrogen
or
obesity.
Mechanistically,
adipocyte
interferes
E2/ESR1
signaling
resulting
transcriptional
repression
of
secreted
phosphoprotein
1
(
Spp1
);
yet
positively
modulates
leptin
expression
by
binding
its
promoter.
abrogation
results
enhanced
SPP1
decreased
secretion
from
both
visceral
BMAds,
concertedly
dictating
stromal
stem
cell
fate
commitment
restoring
type
H
vessel
formation,
constituting
feed-forward
loop
for
formation.
Pharmacological
inhibition
protects
obese
mice
against
loss
high
adiposity.
Thus,
our
findings
highlight
therapeutic
approach
via
targeting
preserve
especially
detrimental
milieu.
Biomaterials,
Journal Year:
2023,
Volume and Issue:
303, P. 122387 - 122387
Published: Nov. 6, 2023
Endochondral
ossification
(ECO),
the
major
process
during
embryogenesis
and
bone
repair,
involves
formation
of
a
cartilaginous
template
remodelled
into
functional
organ.
Adipose-derived
stromal
cells
(ASC),
non-skeletal
multipotent
progenitors
from
vascular
fraction
(SVF)
human
adipose
tissue,
were
shown
to
recapitulate
ECO
generate
organs
in
vivo
when
primed
hypertrophic
cartilage
tissue
(HCT)
vitro.
However,
reproducibility
was
limited
triggers
remain
unknown.
We
studied
effect
expansion
maturation
HCT
on
induction
process.
SVF
or
expanded
ASC
seeded
onto
collagen
sponges,
cultured
chondrogenic
medium
for
3–6
weeks
implanted
ectopically
nude
mice
evaluate
their
bone-forming
capacities.
all
tested
donors
formed
mature
3
whereas
needed
4–5
weeks.
A
longer
increased
degree
HCT,
with
gradually
denser
matrix
mineralization.
This
highly
predictive
capacity
vivo,
achieved
only
an
intermediate
degree.
In
parallel,
expanding
also
resulted
enrichment
characterized
by
rapid
change
proteomic
profile
quiescent
proliferative
state.
Inducing
quiescence
rescued
potential.
Our
findings
emphasize
role
monolayer
provides
simple,
yet
reproducible
effective
approach
be
specific
clinical
models.
Frontiers in Cell and Developmental Biology,
Journal Year:
2025,
Volume and Issue:
13
Published: Jan. 27, 2025
Background
A
significant
number
of
platelet
concentrates
(PCs)
is
discarded
daily
in
blood
banks
due
to
limited
shelf
life.
Human
lysate
(HPL),
derived
from
expired
PCs,
has
gained
attention
as
an
ethical
and
sustainable
cell
culture
media
supplement
biomedical
research
therapy
production.
However,
HPL
subject
decisive
disadvantages
such
batch
differences
lack
storage
stability.
To
overcome
these
limitations
enhance
the
applicability
HPL,
we
developed
manufacturing
protocol
including
a
lyophilization
process.
The
aim
this
study
was
investigate
influence
on
parameters
quality
control,
growth
factor
concentrations
human
mesenchymal
stromal
cells
(hMSCs).
Methods
We
performed
paired
comparison
six
batches
lyophilized
(L-HPL)
regarding
pH,
total
protein,
osmolality,
sodium,
potassium
chloride
concentration.
Concentrations
11
factors
cytokines
were
compared
between
L-HPL.
Additionally,
determined
yield,
proliferation
capacity,
viability
trilineage
differentiation
potential
hMSCs
following
expansion
HPL-
L-HPL-supplemented
media.
Results
Quantification
revealed
non-altered
osmolality
slightly
lower
sodium
L-HPL
HPL.
Growth
cytokine
did
not
differ
Cell
division
cycles
cultured
either
or
L-HPL-containing
comparable.
Cells
differentiated
medium
containing
showed
higher
capacity
for
osteogenic
differentiation,
while
adipogenic
chondrogenic
potentials
remained
unchanged.
Conclusion
successfully
method
produce
well-applicable
with
reveal
any
relevant
control
routine
testing,
hMSC
functionality,
demonstrating
suitability
supplement.
These
results
emphasize
alternative
animal-derived
serum
products
drug
development.
Cells,
Journal Year:
2022,
Volume and Issue:
11(6), P. 946 - 946
Published: March 10, 2022
Donor
variation
is
a
prominent
critical
issue
limiting
the
applicability
of
cell-based
therapies.
We
hypothesized
that
batch
effects
during
propagation
bone
marrow
stromal
cells
(BMSCs)
in
human
platelet
lysate
(hPL),
replacing
fetal
bovine
serum
(FBS),
can
affect
phenotypic
and
functional
variability.
therefore
investigated
impact
donor
variation,
hPL-
vs.
FBS-driven
exhaustive
proliferation,
on
BMSC
epigenome,
transcriptome,
phenotype,
coagulation
risk
osteochondral
regenerative
function.
Notably,
hPL
significantly
increased
created
different
gene
expression
trajectories
distinct
surface
marker
signatures,
already
after
just
one
passage.
confirmed
declining
proliferative
potential
FBS-expanded
challenge.
Flow
cytometry
verified
canonical
fibroblastic
phenotype
culture-expanded
BMSCs.
observed
limited
DNA
methylation,
preferentially
cultures,
irrespective
culture
duration.
The
clotting
over
time.
Moreover,
expansion
xenogenic
resulted
significant
loss
function
3D
cartilage
disk
formation
risk.
Superior
chondrogenic
under
hPL-conditions
was
maintained
culture.
blood
group
isoagglutinins
had
minor
These
data
demonstrate
pronounced
due
to
factors,
partly
outcompeting
