SLAS DISCOVERY,
Journal Year:
2023,
Volume and Issue:
28(7), P. 292 - 305
Published: Sept. 3, 2023
The
field
of
high
content
imaging
has
steadily
evolved
and
expanded
substantially
across
many
industry
academic
research
institutions
since
it
was
first
described
in
the
early
1990's.
High
refers
to
automated
acquisition
analysis
microscopic
images
from
a
variety
biological
sample
types.
Integration
microscopes
with
multiwell
plate
handling
robotics
enables
be
performed
at
scale
support
medium-
high-throughput
screening
pharmacological,
genetic
diverse
environmental
perturbations
upon
complex
systems
ranging
2D
cell
cultures
3D
tissue
organoids
small
model
organisms.
In
this
perspective
article
authors
provide
collective
view
on
following
key
discussion
points
relevant
evolution
imaging:•
Evolution
impact
imaging:
An
perspective•
image
analysis•
data
pipelines
towards
multiparametric
phenotypic
profiling
applications•
role
integration
multiomics•
repositories
sharing
standards•
Future
hardware
software
•
applications
multiomics
standards
Advanced Healthcare Materials,
Journal Year:
2020,
Volume and Issue:
9(23)
Published: July 30, 2020
Abstract
Multi‐cellular
spheroids
are
formed
as
a
3D
structure
with
dense
cell–cell/cell–extracellular
matrix
interactions,
and
thus,
have
been
widely
utilized
implantable
therapeutics
various
ex
vivo
tissue
models
in
engineering.
In
principle,
spheroid
culture
methods
maximize
cell–cell
cohesion
induce
spontaneous
cellular
assembly
while
minimizing
interactions
substrates
by
using
physical
forces
such
gravitational
or
centrifugal
forces,
protein‐repellant
biomaterials,
micro‐structured
surfaces.
addition,
biofunctional
materials
including
magnetic
nanoparticles,
polymer
microspheres,
nanofiber
particles
combined
cells
to
harvest
composite
spheroids,
accelerate
formation,
increase
the
mechanical
properties
viability
of
direct
differentiation
stem
into
desirable
cell
types.
Biocompatible
hydrogels
developed
produce
microgels
for
fabrication
size‐controlled
high
efficiency.
Recently,
further
engineered
fabricate
structurally
functionally
reliable
vitro
artificial
tissues
desired
shape
enhanced
specific
biological
functions.
This
paper
reviews
overall
characteristics
general/advanced
techniques.
Significant
roles
functional
biomaterials
advanced
engineering
emphasis
on
use
reconstruction
also
thoroughly
discussed.
Small,
Journal Year:
2020,
Volume and Issue:
16(13)
Published: Feb. 20, 2020
Abstract
Highly
vascularized
complex
liver
tissue
is
generally
divided
into
lobes,
lobules,
hepatocytes,
and
sinusoids,
which
can
be
viewed
under
different
types
of
lens
from
the
micro‐
to
macro‐scale.
To
engineer
multiscaled
heterogeneous
tissues,
a
sophisticated
rapid
engineering
approach
required,
such
as
advanced
3D
bioprinting.
In
this
study,
preset
extrusion
bioprinting
technique,
create
heterogeneous,
multicellular,
multimaterial
structures
simultaneously,
utilized
for
creating
hepatic
lobule
(≈1
mm)
array.
The
fabricated
lobules
include
cells,
endothelial
lumen.
cells
surround
exterior
lumen,
finally,
become
interconnected
with
each
other.
Compared
cell/endothelial
cell
mixtures,
shows
higher
albumin
secretion,
urea
production,
albumin,
MRP2,
CD31
protein
levels,
well
as,
cytochrome
P450
enzyme
activity.
It
found
that
type
spatial
patterning
in
bioink
accelerates
cellular
organization,
could
preserve
structural
integrity
improve
functions.
conclusion,
extruded
within
highly
construct
are
successfully
constructed,
enabling
both
macro‐scale
fabrication,
support
creation
large
constructs
multiscale
engineering.
Clinical and Translational Science,
Journal Year:
2021,
Volume and Issue:
14(5), P. 1659 - 1680
Published: May 13, 2021
Abstract
Nonclinical
testing
has
served
as
a
foundation
for
evaluating
potential
risks
and
effectiveness
of
investigational
new
drugs
in
humans.
However,
the
current
two‐dimensional
(2D)
vitro
cell
culture
systems
cannot
accurately
depict
simulate
rich
environment
complex
processes
observed
vivo,
whereas
animal
studies
present
significant
drawbacks
with
inherited
species‐specific
differences
low
throughput
increased
demands.
To
improve
nonclinical
prediction
drug
safety
efficacy,
researchers
continue
to
develop
novel
models
evaluate
promote
use
improved
cell‐
organ‐based
assays
more
accurate
representation
human
susceptibility
response.
Among
others,
three‐dimensional
(3D)
physiologically
relevant
cellular
microenvironment
offer
great
promise
assessing
disposition
pharmacokinetics
(PKs)
that
influence
efficacy
from
an
early
stage
development.
Currently,
there
are
numerous
different
types
3D
systems,
simple
spheroids
complicated
organoids
organs‐on‐chips,
single‐cell
type
static
co‐culture
equipped
microfluidic
flow
control
well
hybrid
combine
2D
biomedical
microelectromechanical
systems.
This
article
reviews
application
challenges
PKs,
safety,
assessment,
provides
focused
discussion
regulatory
perspectives
on
liver‐,
intestine‐,
kidney‐,
neuron‐based
models.
Toxicology,
Journal Year:
2021,
Volume and Issue:
450, P. 152667 - 152667
Published: Jan. 8, 2021
We
report
the
development,
automation
and
validation
of
a
3D,
microfluidic
liver-on-a-chip
for
high
throughput
hepatotoxicity
screening,
OrganoPlate
LiverTox™.
The
model
is
comprised
aggregates
induced
pluripotent
stem
cell
(iPSC)-derived
hepatocytes
(iHep)
seeded
in
an
extracellular
matrix
organ
channel
co-cultured
with
endothelial
cells
THP-1
monoblasts
differentiated
to
macrophages
vascular
96
well
Mimetas
2-lane.
A
key
component
screening
we
protocol
seed,
dose,
collect
replenish
media
add
assay
reagents
2-lane
using
standard
laboratory
liquid
handling
robot.
combination
secretome
measurements
image-based
analysis
was
used
demonstrate
stable
15
day
viability,
albumin
urea
secretion.
Over
same
time-period,
CYP3A4
activity
increased
alpha-fetoprotein
secretion
decreased
suggesting
further
maturation
iHeps.
Troglitazone,
clinical
hepatotoxin,
chosen
as
control
compound
studies.
Albumin,
urea,
hepatocyte
nuclear
size
viability
staining
provided
Robust
Z'factors
>
0.2
plates
treated
72
h
180
μM
troglitazone
compared
vehicle
control.
most
robust
statistic
Z'
factor
=
0.6.
small
library
159
compounds
known
liver
effects
added
LiverTox
at
50
Toxicological
Prioritization
scores
were
calculated.
follow
up
dose-response
evaluation
select
hits
revealed
be
sensitive
calculating
TC50
values.
This
platform
provides
robust,
novel
which
can
screening.
Biomolecules,
Journal Year:
2024,
Volume and Issue:
14(1), P. 99 - 99
Published: Jan. 12, 2024
Drug
metabolism
is
a
major
determinant
of
drug
concentrations
in
the
body.
Drug-drug
interactions
(DDIs)
caused
by
co-administration
multiple
drugs
can
lead
to
alteration
exposure
victim
drug,
raising
safety
or
effectiveness
concerns.
Assessment
DDI
potential
starts
with
vitro
experiments
determine
kinetic
parameters
and
identify
risks
associated
use
comedication
that
inform
future
clinical
studies.
The
diverse
range
experimental
models
techniques
has
significantly
contributed
examination
DDIs.
Cytochrome
P450
(CYP)
enzymes
are
responsible
for
biotransformation
many
on
market,
making
them
frequently
implicated
Consequently,
there
been
growing
focus
assessment
risk
CYPs.
This
review
article
provides
mechanistic
insights
underlying
CYP
inhibition/induction
an
overview
CYP-mediated
Toxicological Sciences,
Journal Year:
2018,
Volume and Issue:
163(2), P. 655 - 665
Published: March 23, 2018
High
failure
rates
of
drug
candidates
in
the
clinics,
restricted-use
warnings
as
well
withdrawals
drugs
postmarketing
stages
are
substantial
concern
for
pharmaceutical
industry
and
drug-induced
liver
injury
(DILI)
constitutes
one
most
frequent
reasons
such
safety
failures.
Importantly,
DILI
cannot
be
accurately
predicted
using
animal
models,
tests
commonly
complemented
with
assessments
human
vitro
systems.
3D
spheroid
cultures
primary
hepatocytes
chemically
defined
conditions,
hereafter
termed
CD-spheroids,
have
recently
emerged
a
microphysiological
model
system
which
retain
their
molecular
phenotypes
hepatic
functions
multiple
weeks
culture.
However,
predictive
power
detection
hepatotoxic
liabilities
has
not
been
systematically
assessed.
Therefore,
we
here
evaluated
hepatotoxicity
123
or
without
direct
implication
clinical
events.
ATP
quantifications
single
endpoint,
distinguished
between
nontoxic
structural
analogues
exceeded
both
sensitivity
specificity
all
previously
published
assays
at
substantially
lower
exposure
levels,
successfully
detecting
69%
compounds
producing
any
false
positive
results
(100%
specificity).
Furthermore,
platform
supports
culture
spheroids
from
preclinical
thereby
allowing
identification
animal-specific
toxicity
We
anticipate
that
CD-spheroids
represent
powerful
versatile
tool
discovery
development
can
reliably
flag
provide
guidance
selection
suitable
models.
Biotechnology Journal,
Journal Year:
2019,
Volume and Issue:
14(7)
Published: April 8, 2019
Recent
research
has
shown
that
the
maintenance
of
relevant
liver
functions
ex
vivo
requires
models
in
which
cells
exhibit
an
vivo-like
phenotype,
often
achieved
by
reconstitution
appropriate
cellular
interactions.
Multiple
different
have
been
presented
differ
utilized,
media,
and
culture
conditions.
Furthermore,
several
technologically
approaches
including
bioreactors,
chips,
plate-based
systems
fluidic
or
static
media
constituting
chemically
diverse
materials.
Using
such
models,
ability
to
predict
drug
metabolism,
toxicity,
functionality
increased
tremendously
as
compared
conventional
vitro
are
cultured
2D
monolayers.
Here,
authors
highlight
important
considerations
for
microphysiological
primary
hepatocyte
culture,
review
current
paradigms,
discuss
their
opportunities
studies
hepatotoxicity,
biology,
disease.
EMBO Molecular Medicine,
Journal Year:
2020,
Volume and Issue:
13(1)
Published: Nov. 12, 2020
There
is
a
critical
need
for
safe
and
effective
drugs
COVID-19.
Only
remdesivir
has
received
authorization
COVID-19
been
shown
to
improve
outcomes
but
not
decrease
mortality.
However,
the
dose
of
limited
by
hepatic
kidney
toxicity.
ACE2
cell
surface
receptor
SARS-CoV-2.
Here,
we
investigated
additive
effect
combination
therapy
using
with
recombinant
soluble
(high/low
dose)
on
Vero
E6
organoids,
targeting
two
different
modalities
SARS-CoV-2
life
cycle:
entry
via
its
intracellular
viral
RNA
replication.
This
treatment
markedly
improved
their
therapeutic
windows
against
in
both
models.
By
single
amino-acid
resolution
screening
haploid
ES
cells,
report
singular
pathway
required
toxicity,
namely,
Adenylate
Kinase
2.
The
data
provided
here
demonstrate
that
combining
targets,
common
strategy
HIV
treatment,
exhibit
strong
effects
at
sub-toxic
concentrations.
Our
lay
groundwork
study
combinatorial
regimens
future
clinical
trials.
AJP Cell Physiology,
Journal Year:
2021,
Volume and Issue:
320(5), P. C822 - C841
Published: Jan. 13, 2021
Adipocytes
are
specialized
cells
with
pleiotropic
roles
in
physiology
and
pathology.
Several
types
of
fat
distinct
metabolic
properties
coexist
various
anatomically
defined
depots
mammals.
White,
beige,
brown
adipocytes
differ
their
handling
lipids
thermogenic
capacity,
promoting
differences
size
morphology.
Moreover,
release
proteins
paracrine
endocrine
functions.
The
intrinsic
pose
specific
challenges
culture.
Mature
float
suspension
culture
due
to
high
triacylglycerol
content
fragile.
a
fully
differentiated
state,
notably
acquirement
the
unilocular
lipid
droplet
white
adipocyte,
has
so
far
not
been
reached
two-dimensional
Cultures
mouse
human-differentiated
preadipocyte
cell
lines
primary
have
established
mimic
white,
adipocytes.
Here,
we
survey
models
mature
adipocyte
survival
describing
main
characteristics,
conditions,
advantages,
limitations.
An
important
development
is
advent
three-dimensional
culture,
adipose
spheroids
that
recapitulate
vivo
function
morphology
depots.
Challenges
for
future
include
isolation
adipose-derived
stem
from
different
anatomic
location
animal
humans
differing
sex,
age,
mass,
pathophysiological
conditions.
Further
understanding
dysfunction
will
be
achieved
through
genetic
manipulation,
CRISPR-mediated
gene
editing.
Capturing
heterogeneity
at
single-cell
level
within
single
depot
key
diversities
cardiometabolic
parameters
among
lean
obese
individuals.