International Journal of Molecular Sciences,
Год журнала:
2023,
Номер
24(7), С. 6244 - 6244
Опубликована: Март 26, 2023
Cardiac
organoids
are
in
vitro
self-organizing
and
three-dimensional
structures
composed
of
multiple
cardiac
cells
(i.e.,
cardiomyocytes,
endothelial
cells,
fibroblasts,
etc.)
with
or
without
biological
scaffolds.
Since
recapitulate
structural
functional
characteristics
the
native
heart
to
a
higher
degree
compared
conventional
two-dimensional
culture
systems,
their
applications,
combination
pluripotent
stem
cell
technologies,
being
widely
expanded
for
investigation
cardiogenesis,
disease
modeling,
drug
screening
development,
regenerative
medicine.
In
this
mini-review,
recent
advances
organoid
technologies
summarized
chronological
order,
focus
on
methodological
points
each
formation.
Further,
current
limitations
future
perspectives
these
promising
systems
also
discussed.
Nature Communications,
Год журнала:
2021,
Номер
12(1)
Опубликована: Авг. 26, 2021
Abstract
Congenital
heart
defects
constitute
the
most
common
human
birth
defect,
however
understanding
of
how
these
disorders
originate
is
limited
by
our
ability
to
model
accurately
in
vitro.
Here
we
report
a
method
generate
developmentally
relevant
organoids
self-assembly
using
pluripotent
stem
cells.
Our
procedure
fully
defined,
efficient,
reproducible,
and
compatible
with
high-content
approaches.
Organoids
are
generated
through
three-step
Wnt
signaling
modulation
strategy
chemical
inhibitors
growth
factors.
Heart
comparable
age-matched
fetal
cardiac
tissues
at
transcriptomic,
structural,
cellular
level.
They
develop
sophisticated
internal
chambers
well-organized
multi-lineage
cell
types,
recapitulate
field
formation
atrioventricular
specification,
complex
vasculature,
exhibit
robust
functional
activity.
We
also
show
that
organoid
platform
can
recreate
metabolic
associated
congenital
defects,
as
demonstrated
an
vitro
pregestational
diabetes-induced
defects.
Cell Reports,
Год журнала:
2023,
Номер
42(5), С. 112322 - 112322
Опубликована: Апрель 26, 2023
Crosstalk
between
cardiac
cells
is
critical
for
heart
performance.
Here
we
show
that
vascular
within
human
organoids
(hCOs)
enhance
their
maturation,
force
of
contraction,
and
utility
in
disease
modeling.
Herein
optimize
our
protocol
to
generate
populations
addition
epicardial,
fibroblast,
cardiomyocyte
self-organize
into
in-vivo-like
structures
hCOs.
We
identify
mechanisms
communication
endothelial
cells,
pericytes,
fibroblasts,
cardiomyocytes
ultimately
contribute
organoid
maturation.
In
particular,
(1)
endothelial-derived
LAMA5
regulates
expression
mature
sarcomeric
proteins
contractility,
(2)
paracrine
platelet-derived
growth
factor
receptor
β
(PDGFRβ)
signaling
from
upregulates
matrix
deposition
augment
hCO
contractile
force.
Finally,
demonstrate
determine
the
magnitude
diastolic
dysfunction
caused
by
inflammatory
factors
a
role
endothelin
driving
dysfunction.
Together
this
study
highlights
importance
models.
Scientific Reports,
Год журнала:
2022,
Номер
12(1)
Опубликована: Окт. 18, 2022
Abstract
Cardiovascular
diseases
remain
the
leading
cause
of
death
worldwide;
hence
there
is
an
increasing
focus
on
developing
physiologically
relevant
in
vitro
cardiovascular
tissue
models
suitable
for
studying
personalized
medicine
and
pre-clinical
tests.
Despite
recent
advances,
that
reproduce
both
complexity
maturation
are
still
limited.
We
have
established
a
scaffold-free
protocol
to
generate
multicellular,
beating
human
cardiac
microtissues
from
hiPSCs—namely
organotypic
(hOCMTs)—that
show
some
degree
self-organization
can
be
cultured
long
term.
This
achieved
by
differentiation
hiPSC
2D
monolayer
culture
towards
lineage,
followed
further
aggregation
low-attachment
dishes
3D.
The
generated
hOCMTs
contain
multiple
cell
types
compose
heart
beat
without
external
stimuli
more
than
100
days.
shown
3D
display
improved
specification,
survival
metabolic
as
compared
standard
differentiation.
also
confirmed
functionality
their
response
cardioactive
drugs
long-term
culture.
Furthermore,
we
demonstrated
they
could
used
study
chemotherapy-induced
cardiotoxicity.
Due
showing
tendency
self-organization,
cellular
heterogeneity,
our
over
extended
time,
confirm
these
constructs
organoids
(hCOs).
help
develop
physiologically-relevant
models,
represent
powerful
platform
future
translational
research
biology.
Circulation Research,
Год журнала:
2022,
Номер
130(12), С. 1780 - 1802
Опубликована: Июнь 9, 2022
An
ensemble
of
in
vitro
cardiac
tissue
models
has
been
developed
over
the
past
several
decades
to
aid
our
understanding
complex
cardiovascular
disorders
using
a
reductionist
approach.
These
approaches
often
rely
on
recapitulating
single
or
multiple
clinically
relevant
end
points
dish
indicative
pathophysiology.
The
possibility
generate
disease-relevant
and
patient-specific
human
induced
pluripotent
stem
cells
further
leveraged
utility
as
screening
tools
at
large
scale.
To
elucidate
biological
mechanisms
models,
it
is
critical
integrate
physiological
cues
form
biochemical,
biophysical,
electromechanical
stimuli
achieve
desired
tissue-like
maturity
for
robust
phenotyping.
Here,
we
review
latest
advances
directed
cell
differentiation
derive
wide
gamut
types,
allow
customization
model
systems,
study
diseased
states
types.
We
also
highlight
recent
progress
development
such
organoids,
microtissues,
engineered
heart
tissues,
microphysiological
systems.
expand
discussion
defining
context
use
selection
currently
available
models.
Last,
discuss
limitations
challenges
with
current
state-of-the-art
future
directions.
Frontiers in Cell and Developmental Biology,
Год журнала:
2022,
Номер
10
Опубликована: Ноя. 21, 2022
Medicine
today
faces
the
combined
challenge
of
an
increasing
number
untreatable
diseases
and
fewer
drugs
reaching
clinic.
While
pharmaceutical
companies
have
increased
in
early
development
entering
phase
I
clinical
trials,
actually
successfully
pass
III
launch
into
market.
In
fact,
only
1
out
every
9
will
launch.
Frontiers in Cell and Developmental Biology,
Год журнала:
2022,
Номер
10
Опубликована: Март 31, 2022
The
emergence
of
human
induced
pluripotent
stem
cells
(hiPSCs)
and
efficient
differentiation
hiPSC-derived
cardiomyocytes
(hiPSC-CMs)
from
diseased
donors
have
the
potential
to
recapitulate
molecular
functional
features
heart.
Although
immaturity
hiPSC-CMs,
including
structure,
gene
expression,
conduct,
ion
channel
density,
Ca
2+
kinetics,
is
a
major
challenge,
various
attempts
promote
maturation
been
effective.
Three-dimensional
cardiac
models
using
hiPSC-CMs
achieved
these
morphological
maturations,
disease
patient-specific
furthered
our
understanding
underlying
mechanisms
effective
therapies
for
diseases.
Aside
diseases
drug
responses,
also
evaluate
safety
efficacy
drugs
in
context
before
candidate
enters
market
many
phases
clinical
trials.
In
fact,
novel
testing
paradigms
suggested
that
can
be
used
better
predict
proarrhythmic
risk
drugs.
this
review,
we
overview
current
strategies
engineered
heart
tissue
with
focus
on
discuss
perspectives
future
directions
real
application
modeling,
development,
trials,
cardiotoxicity
tests.