Cells,
Journal Year:
2024,
Volume and Issue:
13(9), P. 745 - 745
Published: April 25, 2024
This
review
delves
into
the
groundbreaking
impact
of
induced
pluripotent
stem
cells
(iPSCs)
and
three-dimensional
organoid
models
in
propelling
forward
neuropathology
research.
With
a
focus
on
neurodegenerative
diseases,
neuromotor
disorders,
related
conditions,
iPSCs
provide
platform
for
personalized
disease
modeling,
holding
significant
potential
regenerative
therapy
drug
discovery.
The
adaptability
iPSCs,
along
with
associated
methodologies,
enables
generation
various
types
neural
cell
differentiations
their
integration
models,
effectively
replicating
complex
tissue
structures
vitro.
Key
advancements
iPSC
protocols,
alongside
careful
selection
donor
types,
are
emphasized
as
critical
steps
harnessing
these
technologies
to
mitigate
tumorigenic
risks
other
hurdles.
Encouragingly,
show
promising
outcomes
therapies,
evidenced
by
successful
application
animal
models.
Advanced Science,
Journal Year:
2021,
Volume and Issue:
8(18)
Published: Aug. 2, 2021
Alzheimer's
disease
(AD)
is
a
progressive
neurodegenerative
with
no
cure.
Huge
efforts
have
been
made
to
develop
anti-AD
drugs
in
the
past
decades.
However,
all
drug
development
programs
for
disease-modifying
therapies
failed.
Possible
reasons
high
failure
rate
include
incomplete
understanding
of
complex
pathophysiology
AD,
especially
sporadic
AD
(sAD),
and
species
difference
between
humans
animal
models
used
preclinical
studies.
In
this
study,
sAD
modeled
using
human
induced
pluripotent
stem
cell
(hiPSC)-derived
3D
brain
organoids.
Because
blood-brain
barrier
(BBB)
leakage
well-known
risk
factor
organoids
are
exposed
serum
mimic
exposure
consequence
BBB
breakdown
patient
brains.
The
serum-exposed
able
recapitulate
AD-like
pathologies,
including
increased
amyloid
beta
(Aβ)
aggregates
phosphorylated
microtubule-associated
tau
protein
(p-Tau)
level,
synaptic
loss,
impaired
neural
network.
Serum
increases
Aβ
p-Tau
levels
through
inducing
beta-secretase
1
(BACE)
glycogen
synthase
kinase-3
alpha
/
(GSK3α/β)
levels,
respectively.
addition,
single-cell
transcriptomic
analysis
reveals
that
reduced
function
both
neurons
astrocytes
immune
response
astrocytes.
organoid-based
model
established
study
can
provide
powerful
platform
mechanistic
therapeutic
future.
MedComm,
Journal Year:
2023,
Volume and Issue:
4(3)
Published: May 17, 2023
Organoids
are
three-dimensional
(3D)
miniaturized
versions
of
organs
or
tissues
that
derived
from
cells
with
stem
potential
and
can
self-organize
differentiate
into
3D
cell
masses,
recapitulating
the
morphology
functions
their
in
vivo
counterparts.
Organoid
culture
is
an
emerging
technology,
organoids
various
tissues,
such
as
brain,
lung,
heart,
liver,
kidney,
have
been
generated.
Compared
traditional
bidimensional
culture,
organoid
systems
unique
advantage
conserving
parental
gene
expression
mutation
characteristics,
well
long-term
maintenance
function
biological
characteristics
vitro.
All
these
features
open
up
new
opportunities
for
drug
discovery,
large-scale
screening,
precision
medicine.
Another
major
application
disease
modeling,
especially
hereditary
diseases
difficult
to
model
vitro
modeled
by
combining
genome
editing
technologies.
Herein,
we
introduce
development
current
advances
technology
field.
We
focus
on
applications
basic
biology
clinical
research,
also
highlight
limitations
future
perspectives.
hope
this
review
provide
a
valuable
reference
developments
organoids.
Signal Transduction and Targeted Therapy,
Journal Year:
2024,
Volume and Issue:
9(1)
Published: April 26, 2024
The
induced
pluripotent
stem
cell
(iPSC)
technology
has
transformed
in
vitro
research
and
holds
great
promise
to
advance
regenerative
medicine.
iPSCs
have
the
capacity
for
an
almost
unlimited
expansion,
are
amenable
genetic
engineering,
can
be
differentiated
into
most
somatic
types.
been
widely
applied
model
human
development
diseases,
perform
drug
screening,
develop
therapies.
In
this
review,
we
outline
key
developments
iPSC
field
highlight
immense
versatility
of
modeling
therapeutic
applications.
We
begin
by
discussing
pivotal
discoveries
that
revealed
potential
a
nucleus
reprogramming
led
successful
generation
iPSCs.
consider
molecular
mechanisms
dynamics
as
well
numerous
methods
available
induce
pluripotency.
Subsequently,
discuss
various
iPSC-based
cellular
models,
from
mono-cultures
single
type
complex
three-dimensional
organoids,
how
these
models
elucidate
diseases.
use
examples
neurological
disorders,
coronavirus
disease
2019
(COVID-19),
cancer
diversity
disease-specific
phenotypes
modeled
using
iPSC-derived
cells.
also
used
high-throughput
screening
toxicity
studies.
Finally,
process
developing
autologous
allogeneic
therapies
their
alleviate
International Journal of Molecular Sciences,
Journal Year:
2023,
Volume and Issue:
24(15), P. 12046 - 12046
Published: July 27, 2023
Although
historically,
the
traditional
bidimensional
in
vitro
cell
system
has
been
widely
used
research,
providing
much
fundamental
information
regarding
cellular
functions
and
signaling
pathways
as
well
nuclear
activities,
simplicity
of
this
does
not
fully
reflect
heterogeneity
complexity
vivo
systems.
From
arises
need
to
use
animals
for
experimental
research
testing.
Nevertheless,
animal
experimentation
presents
various
aspects
complexity,
such
ethical
issues,
which
led
Russell
Burch
1959
formulate
3R
(Replacement,
Reduction,
Refinement)
principle,
underlying
urgent
introduce
non-animal-based
methods
research.
Considering
this,
three-dimensional
(3D)
models
emerged
scientific
community
a
bridge
between
models,
allowing
achievement
differentiation
while
avoiding
The
purpose
review
is
provide
general
overview
most
common
establish
3D
culture
discuss
their
promising
applications.
Three-dimensional
cultures
have
employed
study
both
organ
physiology
diseases;
moreover,
they
represent
valuable
tool
studying
many
cancer.
Finally,
possibility
using
drug
screening
regenerative
medicine
paves
way
development
new
therapeutic
opportunities
diseases.
Nature Communications,
Journal Year:
2024,
Volume and Issue:
15(1)
Published: March 12, 2024
Abstract
Developing
diagnostics
and
treatments
for
neurodegenerative
diseases
(NDs)
is
challenging
due
to
multifactorial
pathogenesis
that
progresses
gradually.
Advanced
in
vitro
systems
recapitulate
patient-like
pathophysiology
are
emerging
as
alternatives
conventional
animal-based
models.
In
this
review,
we
explore
the
interconnected
pathogenic
features
of
different
types
ND,
discuss
general
strategy
modelling
NDs
using
a
microfluidic
chip,
introduce
organoid-on-a-chip
next
advanced
relevant
model.
Lastly,
overview
how
these
models
being
applied
academic
industrial
drug
development.
The
integration
chips,
stem
cells,
biotechnological
devices
promises
provide
valuable
insights
biomedical
research
developing
diagnostic
therapeutic
solutions
NDs.
Annals of Neurology,
Journal Year:
2025,
Volume and Issue:
unknown
Published: Jan. 28, 2025
Objective
Progressive
Supranuclear
Palsy
(PSP)
is
a
severe
neurodegenerative
disease
characterized
by
tangles
of
hyperphosphorylated
tau
protein
and
tufted
astrocytes.
Developing
treatments
for
PSP
challenging
due
to
the
lack
models
reproducing
its
key
pathological
features.
This
study
aimed
model
sporadic
PSP‐Richardson's
syndrome
(PSP‐RS)
using
multi‐donor
midbrain
organoids
(MOs).
Methods
The
MOs
were
generated
pooling
induced
pluripotent
stem
cells
(iPSCs)
from
4
patients
with
probable
PSP‐RS
compared
them
3
healthy
control
(HC)
subjects.
We
performed
comprehensive
analyses
over
120
days
assess
neuronal
death,
reactive
gliosis,
accumulation
4R‐tau
forms
(pThr231,
pSer396,
pThr181,
pSer202/pThr205
[AT8])
immunofluorescence
microscopy
Western
blot.
On
day
90,
immunohistochemical
analysis
pSer396
AT8
antibodies
was
conducted
pathology.
Results
PSP‐derived
showed
progressive
size
reduction
HC‐derived
MOs,
linked
upregulated
apoptosis‐related
mRNA
markers.
Dopaminergic
neuron
degeneration
marked
decreased
tyrosine
hydroxylase
(TH)
increased
neurofilament
light
chain
(NfL).
Immunofluorescence
blot
revealed
all
investigated
peak
at
90
days,
along
significant
rise
in
GFAP‐positive
MOs.
Immunochemistry
confirmed
typical
histological
alterations,
such
as
neurofibrillary
tufted‐shaped
astrocytes,
absent
organoids.
Interpretation
developed
robust
vitro
molecular
histologic
features
disease.
result
holds
promise
advancing
basic
clinical
research
PSP,
paving
way
diagnosis
identification
novel
therapeutic
targets.
ANN
NEUROL
2025
Trends in Molecular Medicine,
Journal Year:
2023,
Volume and Issue:
29(8), P. 659 - 672
Published: June 22, 2023
Progression
of
Alzheimer's
disease
(AD)
entails
deterioration
or
aberrant
function
multiple
brain
cell
types,
eventually
leading
to
neurodegeneration
and
cognitive
decline.
Defining
how
complex
cell-cell
interactions
become
dysregulated
in
AD
requires
novel
human
cell-based
vitro
platforms
that
could
recapitulate
the
intricate
cytoarchitecture
diversity
brain.
Brain
organoids
(BOs)
are
3D
self-organizing
tissues
partially
resemble
architecture
can
AD-relevant
pathology.
In
this
review,
we
highlight
versatile
applications
different
types
BOs
model
pathogenesis,
including
amyloid-β
tau
aggregation,
neuroinflammation,
myelin
breakdown,
vascular
dysfunction,
other
phenotypes,
as
well
accelerate
therapeutic
development
for
AD.
Neural Regeneration Research,
Journal Year:
2023,
Volume and Issue:
0(0), P. 0 - 0
Published: Jan. 1, 2023
At
the
level
of
in
vitro
drug
screening,
development
a
phenotypic
analysis
system
with
high-content
screening
at
core
provides
strong
platform
to
support
high-throughput
screening.
There
are
few
systematic
reports
on
brain
organoids,
as
new
three-dimensional
model,
terms
model
stability,
key
fingerprint,
and
schemes,
particularly
regarding
strategies
for
massive
numbers
traditional
Chinese
medicine
monomers.
This
paper
reviews
organoids
advantages
over
induced
neurons
or
cells
simulated
diseases.
The
also
highlights
prospects
from
induction
criteria
schemes
based
characteristics
application
system.
Stem Cell Research & Therapy,
Journal Year:
2024,
Volume and Issue:
15(1)
Published: May 7, 2024
Abstract
Background
Alzheimer’s
disease
(AD)
is
a
prevalent
form
of
dementia
leading
to
memory
loss,
reduced
cognitive
and
linguistic
abilities,
decreased
self-care.
Current
AD
treatments
aim
relieve
symptoms
slow
progression,
but
cure
elusive
due
limited
understanding
the
underlying
mechanisms.
Main
content
Stem
cell
technology
has
potential
revolutionize
research.
With
ability
self-renew
differentiate
into
various
types,
stem
cells
are
valuable
tools
for
modeling,
drug
screening,
therapy.
Recent
advances
have
broadened
our
beyond
deposition
amyloidβ
(Aβ)
or
tau
proteins
in
encompass
risk
genes,
immune
system
disorders,
neuron–glia
mis-communication,
relying
heavily
on
cell-derived
models.
These
cell-based
models
(e.g.,
organoids
microfluidic
chips)
simulate
vivo
pathological
processes
with
extraordinary
spatial
temporal
resolution.
technologies
alleviate
pathology
through
pathways,
including
immunomodulation,
replacement
damaged
neurons,
neurotrophic
support.
In
recent
years,
transplantation
glial
like
oligodendrocytes
infusion
exosomes
become
hot
research
topics.
Conclusion
Although
therapies
face
several
challenges,
such
as
extended
culture
time
low
differentiation
efficiency,
they
still
show
considerable
treatment
likely
preferred
International Journal of Molecular Sciences,
Journal Year:
2024,
Volume and Issue:
25(4), P. 2392 - 2392
Published: Feb. 18, 2024
Induced
pluripotent
stem
cells
(iPSCs)
are
derived
from
reprogrammed
adult
somatic
cells.
These
manipulated
in
vitro
to
express
genes
and
factors
essential
for
acquiring
maintaining
embryonic
cell
(ESC)
properties.
This
technology
is
widely
applied
many
fields,
much
attention
has
been
given
developing
iPSC-based
disease
models
validate
drug
discovery
platforms
study
the
pathophysiological
molecular
processes
underlying
onset.
Especially
neurological
diseases,
there
a
great
need
technological
research,
as
these
can
be
obtained
each
patient
carry
individual’s
bulk
of
genetic
mutations
unique
Moreover,
iPSCs
differentiate
into
multiple
types.
characteristics,
since
diseases
affected
by
limited
access
injury
sites,
composed
various
types,
complexity
reproducing
brain’s
anatomy,
challenges
postmortem
culture,
ethical
issues.
Neurodegenerative
strongly
impact
global
health
due
their
high
incidence,
symptom
severity,
lack
effective
therapies.
Recently,
analyses
using
specific,
confirmed
efficacy
testing
drugs.
review
summarizes
advances
iPSC
used
modelling
testing,
with
primary
focus
on
neurodegenerative
including
Parkinson’s
Alzheimer’s
diseases.