Current Stem Cell Research & Therapy,
Год журнала:
2023,
Номер
19(10), С. 1303 - 1311
Опубликована: Окт. 17, 2023
In
the
last
decade,
liver
diseases
with
high
mortality
rates
have
become
one
of
most
important
health
problems
in
world.
Organ
transplantation
is
currently
considered
effective
treatment
for
compensatory
failure.
An
increasing
number
patients
and
shortage
donors
has
led
to
attention
reconstructive
medicine
methods
researchers.
The
biggest
challenge
development
drugs
chronic
disease
lack
a
suitable
preclinical
model
that
can
mimic
microenvironment
problems.
Organoid
technology
rapidly
evolving
field
enables
researchers
reconstruct,
evaluate,
manipulate
intricate
biological
processes
Various
control
strategies
are
available
for
building
fluorogenic
probes
to
visualize
biological
events
in
terms
of
a
fluorescence
change.
Here,
we
performed
the
time-dependent
density
functional
theory
(TD-DFT)
computational
analysis
twisted
intramolecular
charge
transfer
(TICT)
process
rhodamine
dyes.
On
basis
results,
designed
and
synthesized
series
dyes
established
quenching
strategy
that
call
steric
repulsion-induced
TICT
(sr-TICT),
which
is
greatly
accelerated
by
simple
twisting.
As
proof
concept
this
design
strategy,
used
it
develop
probe,
2-Me
PeER
(pentyloxyethylrhodamine),
N
-dealkylation
activity
CYP3A4.
We
applied
CYP3A4
activity–based
fluorescence-activated
cell
sorting
(FACS),
providing
access
homogeneous,
highly
human-induced
pluripotent
stem
(hiPSC)–derived
hepatocytes
intestinal
epithelial
cells.
Our
results
suggest
sr-TICT
represents
general
method
probes.
Acta Biomaterialia,
Год журнала:
2025,
Номер
unknown
Опубликована: Март 1, 2025
In
vitro
human
liver
models
are
indispensable
for
compound
metabolism/toxicity
screening,
disease
modeling,
and
regenerative
medicine.
While
induced
pluripotent
stem
cell-derived
hepatocyte-like
cells
(iHeps)
mitigate
the
sourcing
limitations
with
primary
hepatocytes
(PHHs),
their
functional
maturity
is
rate-limiting
application
use.
During
development,
immature
hepatoblasts
interact
different
non-parenchymal
cell
(NPC)
types,
such
as
mesenchyme
endothelia,
in
a
spatiotemporal
manner
to
progress
through
maturation.
Modeling
interactions
critical
elucidate
key
regulators
of
iHep
Here,
we
utilized
high-throughput
droplet
microfluidics
encapsulate
iHeps
within
monodisperse
collagen
I
microgels
(Ø
∼
250µm),
which
were
coated
NPCs
generate
'microtissues'
placed
microwells
multiwell
plates.
Embryonic
fibroblasts
sinusoidal
endothelial
(LSECs)
highest
level
maturation
over
4+
weeks
culture
compared
adult
hepatic
stellate
(myofibroblastic),
portal
fibroblasts,
dermal
umbilical
vein
cells.
Combining
microtissues
plates
Transwell
inserts
containing
NPC
types
enabled
modeling
dynamic
heterotypic
signaling
on
maturation;
introducing
embryonic
fibroblast
first,
followed
by
LSECs,
led
Unique
cytokine
secretion
profiles
detected
across
top-performing
microtissue
configurations;
stromal-derived
factor-1
alpha
was
validated
one
factor
that
enhanced
Lastly,
gene
expression
patterns
regulatory
networks
showed
PHH-like
LSEC/iHep
iHep-only
microtissues.
Overall,
useful
elucidating
microenvironmental
determinants
future
use
downstream
applications.
STATEMENT
OF
SIGNIFICANCE:
We
3D
role
several
culture.
observed
significantly
(LSEC)
non-liver
The
achieved
when
mesenchymal
stimulation
introduced
LSEC
stimulation.
liver-like
signatures.
Ultimately,
can
be
cellular
molecular
maturation,
Frontiers in Pharmacology,
Год журнала:
2023,
Номер
14
Опубликована: Июнь 28, 2023
The
liver
is
the
primary
organ
responsible
for
detoxification
and
metabolism
of
drugs.
To
date,
a
lack
preclinical
models
that
accurately
emulate
drug
by
human
presents
significant
challenge
in
development
pipeline,
particularly
predicting
efficacy
toxicity.
In
recent
years,
emerging
microfluidic-based
organ-on-a-chip
(OoC)
technologies,
combined
with
induced
pluripotent
stem
cell
(hiPSC)
technology,
present
promising
avenue
complete
recapitulation
biology
patient-specific
manner.
However,
hiPSC-derived
organoids
liver-on-a-chip
have
so
far
failed
to
sufficiently
express
cytochrome
P450
monooxygenase
(CYP450)
enzymes,
key
enzymes
involved
first-pass
metabolism,
which
limits
effectiveness
translatability
these
studies.
This
review
explores
potential
innovative
organoid
OoC
technologies
studying
discusses
their
existing
drawbacks,
such
as
low
expression
CYP450
genes.
Finally,
we
postulate
approaches
enhancing
hope
paving
way
toward
developing
novel,
fully
representative
drug-metabolism
models.
Frontiers in Bioengineering and Biotechnology,
Год журнала:
2024,
Номер
12
Опубликована: Фев. 7, 2024
Liver
bioengineering
stands
as
a
prominent
alternative
to
conventional
hepatic
transplantation.
Through
liver
decellularization
and/or
bioprinting,
researchers
can
generate
acellular
scaffolds
overcome
immune
rejection,
genetic
manipulation,
and
ethical
concerns
that
often
accompany
traditional
transplantation
methods,
in
vivo
regeneration,
xenotransplantation.
Hepatic
cell
lines
derived
from
induced
pluripotent
stem
cells
(iPSCs)
repopulate
decellularized
bioprinted
scaffolds,
producing
an
increasingly
functional
organ
potentially
suitable
for
autologous
use.
In
this
mini-review,
we
overview
recent
advancements
vitro
hepatocyte
differentiation
protocols,
shedding
light
on
their
pivotal
role
recellularization
thereby
offering
novel
source
Finally,
identify
future
directions
research
may
allow
the
implementation
of
these
systems
diverse
applications,
including
drug
screening
disease
modeling.
Stem Cells,
Год журнала:
2023,
Номер
41(11), С. 1076 - 1088
Опубликована: Авг. 22, 2023
Human
pluripotent
stem
cell
(hPSC)-derived
hepatocyte-like
cells
(HLCs)
hold
great
promise
for
liver
disease
modeling,
drug
discovery,
and
toxicity
screens.
Yet,
several
hurdles
still
need
to
be
overcome,
including
among
others
decrease
in
the
cost
of
goods
generate
HLCs
automation
differentiation
process.
We
here
describe
that
use
an
automated
liquid
handling
system
results
highly
reproducible
HLC
from
hPSCs.
This
enabled
us
screen
92
chemicals
replace
expensive
growth
factors
at
each
step
protocol
reduce
by
approximately
79%.
In
addition,
we
also
evaluated
recombinant
extracellular
matrices
Matrigel.
demonstrated
hPSCs
on
Laminin-521
using
optimized
small
molecule
combination
resulted
were
transcriptionally
identical
generated
factor
combinations.
created
secreted
similar
amounts
albumin
urea,
relatively
low
concentrations
alfa-fetoprotein,
displayed
CYP3A4
functionality,
a
susceptibility
as
with
cocktails.
The
broad
applicability
new
was
4
different
hPSC
lines.
allowed
creation
scalable,
xeno-free,
cost-efficient
hPSC-derived
culture,
suitable
high
throughput
modeling
screenings,
or
even
regenerative
therapies.
International Journal of Health Sciences,
Год журнала:
2024,
Номер
8(S1), С. 972 - 998
Опубликована: Авг. 5, 2024
Organoids
are
three-dimensional
(3D)
cell
culture
systems
derived
from
human
pluripotent
stem
cells
or
organotypic
differentiation,
replicating
the
complex
interactions
and
functionalities
of
actual
organs.
These
offer
significant
advantages
for
studying
tissue
organ
biology,
addressing
limitations
animal
models
related
to
sample
accessibility
ethical
concerns.
Liver
organoids,
in
particular,
advanced
developed
study
hepatic
phenotypes,
encompassing
various
types
enabling
detailed
investigation
cellular,
molecular,
genetic
aspects
liver
diseases,
drug
metabolism,
protein
secretion.
They
hold
promise
fundamental
research,
discovery,
regenerative
medicine
applications.
Despite
their
potential,
organoids
face
such
as
simplicity,
lack
high-fidelity
types,
flexibility,
atypical
physiology.
Enhancements
liver-like
surrogates,
incorporating
vivo-like
architecture,
along
with
advancements
microfluidic
chip
technology,
expected
improve
disease,
toxicity,
paving
way
new
treatments.
This
review
will
provide
an
overview
history
development
current
progress,
challenges,
applications,
future
prospects
field
personalized
medicine.
