Pump‐Less, Recirculating Organ‐on‐Chip (rOoC) Platform to Model the Metabolic Crosstalk between Islets and Liver
Advanced Healthcare Materials,
Год журнала:
2024,
Номер
13(13)
Опубликована: Янв. 15, 2024
Abstract
Type
2
diabetes
mellitus
(T2DM),
obesity,
and
metabolic
dysfunction‐associated
steatotic
liver
disease
(MASLD)
are
epidemiologically
correlated
disorders
with
a
worldwide
growing
prevalence.
While
the
mechanisms
leading
to
onset
development
of
these
conditions
not
fully
understood,
predictive
tissue
representations
for
studying
coordinated
interactions
between
central
organs
that
regulate
energy
metabolism,
particularly
pancreatic
islets,
needed.
Here,
dual
pump‐less
recirculating
organ‐on‐chip
platform
combines
human
pluripotent
stem
cell
(sc)‐derived
sc‐liver
sc‐islet
organoids
is
presented.
The
reproduces
key
aspects
cross‐talk
both
organs,
including
glucose
levels
selected
hormones,
supports
viability
functionality
while
preserving
reduced
release
pro‐inflammatory
cytokines.
In
model
disruption
in
response
treatment
high
lipids
fructose,
exhibit
hallmarks
steatosis
insulin
resistance,
sc‐islets
produce
cytokines
on‐chip.
Finally,
known
effects
anti‐diabetic
drugs
Taken
together,
provides
basis
functional
studies
T2DM,
MASLD
on‐chip,
as
well
testing
potential
therapeutic
interventions.
Язык: Английский
A Microphysiological Model of Progressive Human Hepatic Insulin Resistance
bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2025,
Номер
unknown
Опубликована: Янв. 8, 2025
Hepatic
insulin
resistance
is
a
fundamental
phenomenon
observed
in
both
Type
2
diabetes
(T2D)
and
metabolic
(dysfunction)
associated
fatty
liver
disease
(MAFLD).
The
relative
contributions
of
nutrients,
hyperinsulinemia,
hormones,
inflammation,
other
cues
are
difficult
to
parse
vivo
as
they
convoluted
by
interplay
between
the
local
systemic
events.
Here,
we
used
well-established
human
microphysiological
system
(MPS)
establish
physiologically-relevant
insulin-responsive
baseline
probe
how
primary
hepatocytes
respond
controlled
perturbations
insulin,
glucose,
free
acids
(FFAs).
Replicate
MPS
were
maintained
media
with
either
200
pM
(normal)
or
800
for
up
3
weeks.
Conditions
standard
glucose
(5.5
mM),
hyperglycemia
(11
mM
glucose),
normal
(20µM)
elevated
FFA
(100
µM),
alone
combination
at
each
concentration,
continuously
reversing
back
after
weeks
simulated
T2D
conditions.
production,
activation
signaling
pathways,
clearance,
transcriptome
analysis,
intracellular
lipid
bile
acid
accumulation
assessed.
Hyperinsulinemia
induces
one
week
exposure,
while
increased
FFAs
significantly
exacerbate
this
phenotype.
Hyperinsulinemia,
along
FFAs,
transcriptionally
predisposes
through
altered
immune
pathways.
phenotypes
hyperinsulinemia
nutrient
overload
partially
reversible
upon
return
normophysiologic
Our
enhanced
vitro
model,
replicating
multiple
aspects
insulin-resistant
condition,
offers
improved
insights
into
mechanisms
relevance
physiology.
many
nutritional,
hormonal,
inflammatory
factors
that
contribute
loss
sensitivity
Diabetes
disorders
patients,
animal
models
fail
capture
all
dimensions
relevant
biology.
We,
therefore,
developed
systems
involving
microfluidic
platform
cultures
time,
under
hormone
concentrations,
analyze
effects
nutrition
(glucose
acids)
together
cause
pathological
features
seen
.
We
found
continually
high
levels
predispose
some
these
features,
reversal
when
nutritional
restored
healthy
values.
Язык: Английский
The fibrosis-4 index and its association with carotid atherosclerosis in type 2 diabetes: a cross-sectional study in China
BMC Cardiovascular Disorders,
Год журнала:
2025,
Номер
25(1)
Опубликована: Янв. 20, 2025
The
medical
community
has
long
been
concerned
about
the
cardiovascular
disease
risk
in
patients
with
type
2
diabetes.
While
liver
fibrosis
scores
were
originally
designed
for
application
individuals
steatosis,
an
increasing
number
of
studies
have
shown
that
they
are
also
associated
risk.
However,
association
between
Fibrosis-4
(Fib-4)
and
carotid
atherosclerosis
(CA)
diabetes
remains
unclear.
aim
this
study
is
to
investigate
Fib-4
index
CA
Type
Additionally,
it
seeks
determine
whether
relationship
influenced
by
factors
including
gender,
age,
body
mass
(BMI),
hypertension,
other
variables.
Screening
based
on
inclusion
exclusion
criteria
identified
2658
hospitalized
Subsequently,
divided
into
three
groups
according
values
(Fib-4
<
1.3,
1.3
≤
2.67,
≥
2.67).
Logistic
regression
analysis
was
then
applied
evaluate
presence
Further
stratified
analyses
conducted
considering
age
(using
60
years
as
threshold),
hypertension
status,
smoking,
alcohol
consumption,
BMI
24
kg/m2
aiming
potential
effect
heterogeneity
within
predefined
subgroups.
ROC
curve
used
predictive
power
value
CA,
increased
CIMT,
plaques.
encompassed
diagnosed
diabetes,
comprising
1441
males
1217
females,
average
56.71
±
10.22
years.
Among
them,
1736
(65.3%)
exhibited
1243
(46.8%)
had
intima-media
thickness
(CIMT),
1273
(47.9%)
manifested
Following
adjustments
various
factors,
prevalence
a
progressive
increase
2.67
groups,
statistically
significant
differences
(P
0.05).
Moreover,
CIMT
plaques
group
remained
significantly
higher
than
after
In
group,
subsequent
drinking,
surpassed
Despite
further
multiple
persisted
yet
difference
lacked
statistical
significance
>
results
indicated
AUC
predicting
0.602
0.001,
95%
CI:
0.579–0.625),
while
0.561
0.540–0.583)
0.580
0.558–0.601),
respectively.
Elevated
levels
1.3)
positively
As
such,
may
serve
biomarker
detection
its
clinical
utility
needs
validation,
particularly
larger
sample
sizes
multicenter
studies.
Язык: Английский
Electromembrane Extraction Provides Unprecedented Selectivity for Drugs in Cell Culture Media Used in Organoid and Organ-on-Chip Systems
Analytical Chemistry,
Год журнала:
2025,
Номер
unknown
Опубликована: Фев. 24, 2025
The
use
of
organoids
and
organ-on-chip
technologies
as
nonanimal
methodologies
in
drug
discovery
personalized
medicine
is
rapidly
expanding.
However,
the
complexity
small
volumes
organoid
culture
samples
present
significant
analytical
challenges,
e.g.,
analysis
using
liquid
chromatography–mass
spectrometry
(LC–MS).
Essentially
an
electrophoresis
across
oil
membrane,
electromembrane
extraction
(EME)
offers
a
promising
approach
for
measuring
drugs,
it
is,
example,
compatible
with
such
formats.
Given
potential
technology,
there
need
to
assess
purity
EME
extracts
ensure
EME's
compatibility
high-throughput,
downstream
analysis.
This
study
evaluates
effectiveness
sample
cleanup
various
common
cell
media
used
organs-on-chips.
were
spiked
90
small-molecule
drugs.
Using
gel
(sodium
dodecyl
sulfate
polyacrylamide
electrophoresis),
high-resolution
nuclear
magnetic
resonance
spectroscopy,
LC–MS,
we
demonstrate
that
provides
exhaustive
removal
unwanted
medium
components
(proteins,
polar
molecules,
apolar/neutral
molecules)
while
selectively
extracting
was
demonstrated
human
stem-cell-derived
liver
organoids,
allowing
simple
detection
monitoring
telltale
cytochrome
P450
metabolism.
Taken
together,
our
observations
highlight
unprecedented
ability
provide
matrixes
technology.
Язык: Английский
From organoids to organoids-on-a-chip: Current applications and challenges in biomedical research
Chinese Medical Journal,
Год журнала:
2025,
Номер
unknown
Опубликована: Фев. 25, 2025
Abstract
The
high
failure
rates
in
clinical
drug
development
based
on
animal
models
highlight
the
urgent
need
for
more
representative
human
biomedical
research.
In
response
to
this
demand,
organoids
and
organ
chips
were
integrated
greater
physiological
relevance
dynamic,
controlled
experimental
conditions.
This
innovative
platform—the
organoids-on-a-chip
technology—shows
great
promise
disease
modeling,
discovery,
personalized
medicine,
attracting
interest
from
researchers,
clinicians,
regulatory
authorities,
industry
stakeholders.
review
traces
evolution
organoids-on-a-chip,
driven
by
necessity
advanced
biological
models.
We
summarize
applications
of
simulating
pathological
phenotypes
therapeutic
evaluation
technology.
section
highlights
how
integrating
technologies
chips,
such
as
microfluidic
systems,
mechanical
stimulation,
sensor
integration,
optimizes
organoid
cell
types,
spatial
structure,
functions,
thereby
expanding
their
applications.
conclude
addressing
current
challenges
offering
insights
into
prospects.
advancement
is
poised
enhance
fidelity,
standardization,
scalability.
Furthermore,
integration
cutting-edge
interdisciplinary
collaborations
will
be
crucial
progression
Язык: Английский
Anti-inflammatory PEGylated bilirubin microneedle patch for diabetes treatment
Applied Materials Today,
Год журнала:
2024,
Номер
39, С. 102295 - 102295
Опубликована: Июнь 15, 2024
Язык: Английский
Cell identity dynamics and insight into insulin secretagogues when employing stem cell-derived islets for disease modeling
Frontiers in Bioengineering and Biotechnology,
Год журнала:
2024,
Номер
12
Опубликована: Июнь 12, 2024
Stem
cell-derived
islets
(SC-islets)
are
not
only
an
unlimited
source
for
cell-based
therapy
of
type
1
diabetes
but
have
also
emerged
as
attractive
material
modeling
and
conducting
screening
treatment
options.
Prior
to
SC-islets
becoming
the
established
standard
disease
drug
development,
it
is
essential
understand
their
response
various
nutrient
sources
in
vitro
.
This
study
demonstrates
enhanced
efficiency
pancreatic
endocrine
cell
differentiation
through
incorporation
WNT
signaling
inhibition
following
definitive
endoderm
stage.
We
identified
a
tri-hormonal
population
within
SC-islets,
which
undergoes
reduction
concurrent
with
emergence
elevated
numbers
glucagon-positive
cells
during
extended
culture.
Over
6-week
period
culture,
consistently
demonstrated
robust
insulin
secretion
glucose
stimulation.
Moreover,
they
manifested
diverse
reactivity
patterns
when
exposed
distinct
exhibited
deviant
glycolytic
metabolic
characteristics
comparison
human
primary
islets.
Although
aberrant
metabolism
trafficking,
evaluation
potential
antidiabetic
drug,
pyruvate
kinase
agonist
known
TEPP46,
significantly
improved
SC-islets.
Overall,
this
provided
identity
dynamics
investigation
prolonged
culturing
,
insights
into
secretagogues.
Associated
advantages
limitations
were
discussed
employing
modeling.
Язык: Английский
A metabolic-dysfunction associated steatotic liver acinus biomimetic induces pancreatic islet dysfunction in a coupled microphysiology system
bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2024,
Номер
unknown
Опубликована: Апрель 26, 2024
Abstract
Preclinical
and
clinical
studies
suggest
that
lipid-induced
hepatic
insulin
resistance
is
a
primary
defect
predisposes
to
dysfunction
in
pancreatic
islets,
implicating
perturbed
liver-pancreas
axis
underlying
the
comorbidity
of
T2DM
MASLD.
To
investigate
this
hypothesis,
we
developed
human
biomimetic
microphysiological
system
(MPS)
coupling
our
vascularized
liver
acinus
MPS
(vLAMPS)
with
islets
on
chip
(PANIS)
enabling
MASLD
progression
islet
be
quantitatively
assessed.
The
modular
design
(vLAMPS-PANIS)
allows
intra-organ
inter-organ
dysregulation
deconvoluted.
When
compared
normal
fasting
(NF)
conditions,
under
early
metabolic
syndrome
(EMS)
standalone
vLAMPS
exhibited
characteristics
stage
MASLD,
while
no
significant
differences
were
observed
PANIS.
In
contrast,
EMS,
coupled
vLAMPS-PANIS
islet-specific
secretome
significantly
dysregulated
glucose
stimulated
secretion
(GSIS)
response
direct
signaling
from
islets.
Correlations
between
several
pairs
vLAMPS-derived
PANIS-derived
secreted
factors
altered
as
NF
mechanistically
connecting
associated
islet-derived
GLP-1
synthesis
regulation.
Since
compatible
patient–specific
iPSCs,
platform
represents
an
important
step
towards
addressing
patient
heterogeneity,
identifying
complex
disease
mechanisms,
advancing
precision
medicine.
Язык: Английский
A metabolic dysfunction-associated steatotic liver acinus biomimetic induces pancreatic islet dysfunction in a coupled microphysiology system
Communications Biology,
Год журнала:
2024,
Номер
7(1)
Опубликована: Окт. 14, 2024
Preclinical
and
clinical
studies
suggest
that
lipid-induced
hepatic
insulin
resistance
is
a
primary
defect
predisposes
to
dysfunction
in
islets,
implicating
perturbed
liver-pancreas
axis
underlying
the
comorbidity
of
T2DM
MASLD.
To
investigate
this
hypothesis,
we
developed
human
biomimetic
microphysiological
system
(MPS)
coupling
our
vascularized
liver
acinus
MPS
(vLAMPS)
with
pancreatic
islet
(PANIS)
enabling
MASLD
progression
be
assessed.
The
modular
design
(vLAMPS-PANIS)
allows
intra-organ
inter-organ
dysregulation
deconvoluted.
When
compared
normal
fasting
(NF)
conditions,
under
early
metabolic
syndrome
(EMS)
standalone
vLAMPS
exhibited
characteristics
stage
MASLD,
while
no
significant
differences
were
observed
PANIS.
In
contrast,
EMS,
coupled
vLAMPS-PANIS
islet-specific
secretome
significantly
dysregulated
glucose
stimulated
secretion
response
direct
signaling
from
islets.
Correlations
between
several
pairs
vLAMPS-derived
PANIS-derived
factors
altered
as
NF
mechanistically
connecting
associated
hepatic-factors
islet-derived
GLP-1
synthesis
regulation.
Since
compatible
patient-specific
iPSCs,
platform
represents
an
important
step
towards
addressing
patient
heterogeneity,
identifying
disease
mechanisms,
advancing
precision
medicine.
A
liver-islet
was
used
T2DM.
This
study
demonstrated
secreted
disrupt
function
potential
mechanisms
along
axis.
Язык: Английский
The Role of Silicon Technology in Organ‐On‐Chip: Current Status and Future Perspective
Advanced Materials Technologies,
Год журнала:
2024,
Номер
unknown
Опубликована: Дек. 11, 2024
Abstract
Organ‐on‐chip
(OoC)
systems
are
microfluidic
in
vitro
platforms
constructed
to
expand
the
current
understanding
of
organ‐level
physiology
and
response.
This
technology
holds
significant
potential
transform
drug
discovery,
precision
medicine,
disease
modeling
while
reducing
animal
model
use.
Recent
developments
OoC
have
shown
great
promise,
demonstrated
using
relatively
simple
designs.
Currently,
consensus
OoC‐related
literature
is
that
future
lies
development
robust
offer
higher
throughput,
improved
customization,
levels
integration
sensing
actuation
modalities.
The
implementation
silicon
micro‐nanofabrication
technologies
can
foster
such
a
transition,
but
application
field
remains
limited.
In
this
review,
an
overview
provided
been
or
be
applied
realization
compact
systems,
with
focus
on
integrated
Emerging
highlighted
for
heterogeneous
silicon‐based
polymer‐based
components
multimodal
platforms.
Finally,
most
promising
avenues
outlined
within
framework
biomedical
research
personalized
medicine.
Язык: Английский