International Journal of Molecular Sciences,
Год журнала:
2020,
Номер
21(17), С. 6215 - 6215
Опубликована: Авг. 27, 2020
Liver
transplantation
is
the
most
common
treatment
for
patients
suffering
from
liver
failure
that
caused
by
congenital
diseases,
infectious
agents,
and
environmental
factors.
Despite
a
high
rate
of
patient
survival
following
transplantation,
organ
availability
remains
key
limiting
factor.
As
such,
research
has
focused
on
different
cell
types
are
capable
repopulating
restoring
function.
The
best
cellular
mix
engrafting
proliferating
over
long-term,
as
well
optimal
immunosuppression
regimens,
remain
to
be
clearly
well-defined.
Hence,
alternative
strategies
in
field
regenerative
medicine
have
been
explored.
Since
discovery
induced
pluripotent
stem
cells
(iPSC)
potential
differentiating
into
broad
spectrum
types,
many
studies
reported
achievement
iPSCs
differentiation
cells,
such
hepatocytes,
cholangiocytes,
endothelial
Kupffer
cells.
In
parallel,
an
increasing
interest
study
self-assemble
or
matrix-guided
three-dimensional
(3D)
organoids
paved
way
functional
bioartificial
livers.
this
review,
we
will
focus
recent
breakthroughs
development
iPSCs-based
major
drawbacks
challenges
need
overcome
future
applications.
Proceedings of the National Academy of Sciences,
Год журнала:
2021,
Номер
118(8)
Опубликована: Фев. 4, 2021
Significance
Human
PSC-derived
iBMECs
have
been
generated
to
study
disease
mechanisms
and
drug
development
for
neurological
disorders.
However,
their
full
transcriptomic
characterization
is
unclear,
which
could
result
in
inaccurate
physiological
studies
of
treatments
with
ineffective
clinical
outcomes.
Utilizing
a
comprehensive
metaanalysis
validated
by
studies,
we
find
that
many
current
protocols
used
generate
produce
homogenous
epithelial
cell
population.
Overexpression
ETS
transcription
factors
reprogram
these
cells
into
phenotypic
endothelial
(rECs)
recapitulate
certain
vascular
functions,
albeit
lacking
expression
some
organotypic
transporter
genes
high
electrical
resistance
vitro.
Nevertheless,
they
represent
crucial
step
toward
the
generation
an
vitro
model
suitable
pharmaceutical
blood–brain
barrier.
Nature Communications,
Год журнала:
2021,
Номер
12(1)
Опубликована: Окт. 8, 2021
Abstract
Parkinson’s
disease
and
related
synucleinopathies
are
characterized
by
the
abnormal
accumulation
of
alpha-synuclein
aggregates,
loss
dopaminergic
neurons,
gliosis
substantia
nigra.
Although
clinical
evidence
in
vitro
studies
indicate
disruption
Blood-Brain
Barrier
disease,
mechanisms
mediating
endothelial
dysfunction
is
not
well
understood.
Here
we
leveraged
Organs-on-Chips
technology
to
develop
a
human
Brain-Chip
representative
nigra
area
brain
containing
astrocytes,
microglia,
pericytes,
microvascular
cells,
cultured
under
fluid
flow.
Our
αSyn
fibril-induced
model
was
capable
reproducing
several
key
aspects
including
phosphorylated
(pSer129-αSyn),
mitochondrial
impairment,
neuroinflammation,
compromised
barrier
function.
This
may
enable
research
into
dynamics
cell-cell
interactions
serve
as
testing
platform
for
target
identification
validation
novel
therapeutics.
Fluids and Barriers of the CNS,
Год журнала:
2020,
Номер
17(1)
Опубликована: Апрель 22, 2020
The
blood-brain
barrier
(BBB)
is
a
critical
component
of
the
central
nervous
system
that
protects
neurons
and
other
cells
brain
parenchyma
from
potentially
harmful
substances
found
in
peripheral
circulation.
Gaining
thorough
understanding
development
function
human
BBB
has
been
hindered
by
lack
relevant
models
given
significant
species
differences
limited
access
to
vivo
tissue.
However,
advances
induced
pluripotent
stem
cell
(iPSC)
organ-chip
technologies
now
allow
us
improve
our
knowledge
both
health
disease.
This
review
focuses
on
recent
progress
modeling
vitro
using
iPSCs.
Since
the
advent
of
organ-on-a-chip,
many
researchers
have
tried
to
mimic
physiology
human
tissue
on
an
engineered
platform.
In
case
brain
tissue,
structural
connections
and
cell-cell
interactions
are
important
factors
for
function.
The
recent
development
brain-on-a-chip
is
effort
those
functional
aspects
within
a
miniaturized
From
this
perspective,
we
provide
overview
trace
development,
especially
in
terms
complexity
high-content/high-throughput
screening
capabilities,
future
perspectives
more
vivo-like
development.
Frontiers in Bioengineering and Biotechnology,
Год журнала:
2020,
Номер
8
Опубликована: Дек. 10, 2020
Organ-on-chip
(OOC)
systems
recapitulate
key
biological
processes
and
responses
in
vitro
exhibited
by
cells,
tissues,
organs
vivo.
Accordingly,
these
models
of
both
health
disease
hold
great
promise
for
improving
fundamental
research,
drug
development,
personalized
medicine,
testing
pharmaceuticals,
food
substances,
pollutants
etc.
Cells
within
the
body
are
exposed
to
biomechanical
stimuli,
nature
which
is
tissue
specific
may
change
with
or
injury.
These
stimuli
regulate
cell
behavior
can
amplify,
annul,
even
reverse
response
a
given
biochemical
cue
candidate.
As
such,
application
an
appropriate
physiological
pathological
environment
essential
successful
recapitulation
vivo
OOC
models.
Here
we
review
current
range
commercially
available
platforms
incorporate
active
stimulation.
We
highlight
recent
findings
demonstrating
importance
including
mechanical
used
development
outline
emerging
factors
cellular
environment.
explore
incorporation
different
organ
identify
areas
where
further
research
required.
Challenges
associated
integration
mechanics
alongside
other
requirements
scaling
increase
throughput
diagnostic
imaging
discussed.
In
summary,
compelling
evidence
demonstrates
that
microphysiological
fully
replicating
physiology
disease.
ABSTRACT
Although
initially
developed
to
replace
animal
testing
in
drug
development,
human
‘organ
on
a
chip’
(organ
chip)
microfluidic
culture
technology
offers
new
tool
for
studying
tissue
development
and
pathophysiology,
which
has
brought
us
one
step
closer
carrying
out
experimentation
vitro.
In
this
Spotlight
article,
I
discuss
the
central
role
that
developmental
biology
played
early
stages
of
organ-chip
technology,
how
these
models
have
led
insights
into
physiology
disease
mechanisms.
Advantages
disadvantages
approach
relative
organoids
other
cell
cultures
are
also
discussed.
Cell Reports,
Год журнала:
2018,
Номер
25(4), С. 1081 - 1096.e6
Опубликована: Окт. 1, 2018
Highlights•Differentiated
HD
and
non-diseased
iPSCs
into
functional
cortical
neurons•HD
iPSC-derived
neurons
display
altered
transcriptomics•HD
morphology•HD
phenotypesSummaryHuntington's
disease
(HD)
is
a
neurodegenerative
caused
by
an
expanded
CAG
repeat
in
the
Huntingtin
(HTT)
gene.
Induced
pluripotent
stem
cell
(iPSC)
models
of
provide
opportunity
to
study
mechanisms
underlying
pathology
disease-relevant
patient
tissues.
Murine
studies
have
demonstrated
that
HTT
intricately
involved
corticogenesis.
However,
effect
mutant
Hungtintin
(mtHTT)
human
corticogenesis
has
not
yet
been
thoroughly
explored.
This
examination
critical,
due
inherent
differences
development
timing
between
humans
mice.
We
therefore
differentiated
neurons.
While
can
successfully
differentiate
toward
fate
culture,
resulting
transcriptomics,
morphological
phenotypes
indicative
HD.Graphical
abstract
