Translational Psychiatry,
Год журнала:
2024,
Номер
14(1)
Опубликована: Янв. 23, 2024
Abstract
Schizophrenia
(SCZ)
is
a
complex
neurodevelopmental
disorder
characterized
by
the
manifestation
of
psychiatric
symptoms
in
early
adulthood.
While
many
research
avenues
into
origins
SCZ
during
brain
development
have
been
explored,
contribution
endothelial/vascular
dysfunction
to
disease
remains
largely
elusive.
To
model
neuropathology
critical
periods
development,
we
utilized
patient-derived
induced
pluripotent
stem
cells
(iPSCs)
generate
3D
cerebral
organoids
and
define
cell-specific
signatures
disease.
Single-cell
RNA
sequencing
revealed
that
while
were
similar
their
macromolecular
diversity
generated
from
healthy
controls
(CTRL),
exhibited
higher
percentage
endothelial
when
normalized
total
cell
numbers.
Additionally,
compared
CTRL,
differential
gene
expression
analysis
significant
enrichment
genes
function
vessel
formation,
vascular
regulation,
inflammatory
response
cells.
In
line
with
these
findings,
data
23
donors
demonstrated
PECAM1
+
microvascular
vessel-like
structures
increased
length
number
comparison
CTRL
organoids.
Furthermore,
report
displayed
paracellular
permeability,
implicating
elevated
activity.
Collectively,
our
identified
altered
patterns,
structural
changes,
enhanced
permeability
models
SCZ.
Hence,
could
play
role
etiology
modulating
developing
blood
barrier
(BBB).
Brain
organoids
have
been
used
to
recapitulate
the
processes
of
brain
development
and
related
diseases.
However,
lack
vasculatures,
which
regulate
neurogenesis
disorders,
limits
utility
organoids.
In
this
study,
we
induced
vessel
organoids,
respectively,
then
fused
two
types
together
obtain
vascularized
The
were
engrafted
with
robust
vascular
network-like
structures
exhibited
increased
number
neural
progenitors,
in
line
possibility
that
vessels
development.
Fusion
also
contained
functional
blood–brain
barrier-like
structures,
as
well
microglial
cells,
a
specific
population
immune
cells
brain.
incorporated
microglia
responded
actively
stimuli
showed
ability
engulfing
synapses.
Thus,
fusion
established
study
allow
modeling
interactions
between
neuronal
non-neuronal
components
vitro,
particularly
vasculature
niche.
Stem Cell Reports,
Год журнала:
2022,
Номер
17(2), С. 307 - 320
Опубликована: Янв. 20, 2022
Neurological
complications
are
common
in
COVID-19.
Although
SARS-CoV-2
has
been
detected
patients'
brain
tissues,
its
entry
routes
and
resulting
consequences
not
well
understood.
Here,
we
show
a
pronounced
upregulation
of
interferon
signaling
pathways
the
neurovascular
unit
fatal
By
investigating
susceptibility
human
induced
pluripotent
stem
cell
(hiPSC)-derived
capillary
endothelial-like
cells
(BCECs)
to
infection,
found
that
BCECs
were
infected
recapitulated
transcriptional
changes
vivo.
While
compromised
their
paracellular
tightness,
basolateral
compartment
transwell
assays
after
apical
suggesting
active
replication
transcellular
transport
virus
across
blood-brain
barrier
(BBB)
vitro.
Moreover,
into
could
be
reduced
by
anti-spike-,
anti-angiotensin-converting
enzyme
2
(ACE2)-,
anti-neuropilin-1
(NRP1)-specific
antibodies
or
transmembrane
protease
serine
subtype
(TMPRSS2)
inhibitor
nafamostat.
Together,
our
data
provide
strong
support
for
BBB
increased
signaling.
Brain,
Год журнала:
2022,
Номер
145(12), С. 4334 - 4348
Опубликована: Янв. 24, 2022
Blood-brain
barrier
(BBB)
breakdown
and
immune
cell
infiltration
into
the
CNS
are
early
hallmarks
of
multiple
sclerosis
(MS).
The
mechanisms
leading
to
BBB
dysfunction
incompletely
understood
generally
thought
be
a
consequence
neuroinflammation.
Here,
we
have
challenged
this
view
asked
if
intrinsic
alterations
in
MS
patients
contribute
pathogenesis.
To
end,
made
use
human
induced
pluripotent
stem
cells
derived
from
healthy
controls
differentiated
them
brain
microvascular
endothelial
(BMEC)-like
as
vitro
model
BBB.
MS-derived
BMEC-like
showed
impaired
junctional
integrity,
properties
efflux
pump
activity
when
compared
controls.
Also,
displayed
an
inflammatory
phenotype
with
increased
adhesion
molecule
expression
interactions.
Activation
Wnt/β-catenin
signalling
progenitor
enhanced
characteristics
reduced
phenotype.
Our
study
provides
evidence
for
impairment
function
that
can
modelled
vitro.
Human
iPSC-derived
thus
suitable
explore
molecular
underpinnings
will
assist
identification
potential
novel
therapeutic
targets
stabilization.
Preservation
of
brain
health
has
emerged
as
a
leading
public
priority
for
the
aging
world
population.
Advances
in
neurovascular
biology
have
revealed
an
intricate
relationship
among
cells,
meninges,
and
hematic
lymphatic
vasculature
(the
neurovasculome)
that
is
highly
relevant
to
maintenance
cognitive
function.
In
this
scientific
statement,
multidisciplinary
team
experts
examines
these
advances,
assesses
their
relevance
disease,
identifies
knowledge
gaps,
provides
future
directions.
Fluids and Barriers of the CNS,
Год журнала:
2023,
Номер
20(1)
Опубликована: Март 28, 2023
Abstract
The
CLDN5
gene
encodes
claudin-5
(CLDN-5)
that
is
expressed
in
endothelial
cells
and
forms
tight
junctions
which
limit
the
passive
diffusions
of
ions
solutes.
blood–brain
barrier
(BBB),
composed
brain
microvascular
associated
pericytes
end-feet
astrocytes,
a
physical
biological
to
maintain
microenvironment.
expression
CLDN-5
tightly
regulated
BBB
by
other
junctional
proteins
supports
from
astrocytes.
most
recent
literature
clearly
shows
compromised
with
decline
increasing
risks
developing
neuropsychiatric
disorders,
epilepsy,
calcification
dementia.
purpose
this
review
summarize
known
diseases
function.
In
first
part
review,
we
highlight
understanding
how
as
well
astrocytes
cells.
We
detail
some
drugs
can
enhance
these
are
being
developed
or
currently
use
treat
decline.
then
summarise
mutagenesis-based
studies
have
facilitated
better
physiological
role
protein
at
demonstrated
functional
consequences
recently
identified
pathogenic
missense
mutation
patients
alternating
hemiplegia
childhood.
This
gain-of-function
CLDN
family
all
others
representing
loss-of-function
mutations
resulting
mis-localization
and/or
attenuated
Finally,
reports
about
dosage-dependent
effect
on
development
neurological
mice
discuss
what
cellular
for
regulation
human
diseases.
Advanced Drug Delivery Reviews,
Год журнала:
2021,
Номер
175, С. 113798 - 113798
Опубликована: Май 18, 2021
Every
year,
cancer
claims
millions
of
lives
around
the
globe.
Unfortunately,
model
systems
that
accurately
mimic
human
oncology
–
a
requirement
for
development
more
effective
therapies
these
patients
remain
elusive.
Tumor
is
an
organ-specific
process
involves
modification
existing
tissue
features,
recruitment
other
cell
types,
and
eventual
metastasis
to
distant
organs.
Recently,
engineered
microfluidic
devices
have
emerged
as
powerful
in
vitro
tool
physiology
pathology
with
organ-specificity.
These
organ-on-chip
platforms
consist
cells
cultured
3D
hydrogels
offer
precise
control
over
geometry,
biological
components,
physiochemical
properties.
Here,
we
review
progress
towards
models
primary
metastatic
tumor
microenvironments.
Despite
field's
infancy,
tumor-on-chip
enabled
discoveries
about
immunobiology
response
therapy.
Future
work
should
focus
on
autologous
or
multi-organ
inclusion
immune
system.
International Journal of Molecular Sciences,
Год журнала:
2021,
Номер
22(14), С. 7710 - 7710
Опубликована: Июль 19, 2021
The
blood-brain
barrier
(BBB)
regulates
the
delivery
of
oxygen
and
important
nutrients
to
brain
through
active
passive
transport
prevents
neurotoxins
from
entering
brain.
It
also
has
a
clearance
function
removes
carbon
dioxide
toxic
metabolites
central
nervous
system
(CNS).
Several
drugs
are
unable
cross
BBB
enter
CNS,
adding
complexity
drug
screens
targeting
disorders.
A
well-functioning
is
essential
for
maintaining
healthy
tissue,
malfunction
BBB,
linked
its
permeability,
results
in
toxins
immune
cells
CNS.
This
impairment
associated
with
variety
neurological
diseases,
including
Alzheimer's
disease
Parkinson's
disease.
Here,
we
summarize
current
knowledge
about
neurodegenerative
diseases.
Furthermore,
focus
on
recent
progress
using
human-induced
pluripotent
stem
cell
(iPSC)-derived
models
study
BBB.
We
review
potential
novel
cell-based
platforms
modeling
address
advances
key
challenges
technology
human
Finally,
highlight
future
directions
this
area.
iScience,
Год журнала:
2022,
Номер
25(8), С. 104813 - 104813
Опубликована: Июль 21, 2022
Species
differences
in
brain
and
blood-brain
barrier
(BBB)
biology
hamper
the
translation
of
findings
from
animal
models
to
humans,
impeding
development
therapeutics
for
diseases.
Here,
we
present
a
human
organotypic
microphysiological
system
(MPS)
that
includes
endothelial-like
cells,
pericytes,
glia,
cortical
neurons
maintains
BBB
permeability
at
vivo
relevant
levels.
This
Brain-Chip
engineered
recapitulate
critical
aspects
complex
interactions
mediate
neuroinflammation
demonstrates
significant
improvements
clinical
mimicry
compared
previously
reported
similar
MPS.
In
comparison
Transwell
culture,
transcriptomic
profiling
displayed
significantly
advanced
similarity
adult
cortex
enrichment
key
neurobiological
pathways.
Exposure
TNF-α
recreated
anticipated
inflammatory
environment
shown
by
glia
activation,
increased
release
proinflammatory
cytokines,
compromised
permeability.
We
report
robust
MPS
mechanistic
understanding
cell-cell
function
during
neuroinflammation.