Proceedings of the National Academy of Sciences,
Год журнала:
2024,
Номер
121(52)
Опубликована: Дек. 20, 2024
The
formation
of
functional
epithelial
tubules
is
critical
for
the
development
and
maintenance
many
organ
systems.
While
mechanisms
tubule
by
cells
are
well
studied,
process
anastomosis—where
connect
to
form
a
continuous
network—remains
poorly
understood.
In
this
study,
we
utilized
single-cell
RNA
sequencing
analyze
embryonic
mouse
kidney
undergoing
anastomosis.
Our
analysis
identified
hepatocyte
growth
factor
(HGF)
as
key
potential
mediator
process.
To
investigate
further,
developed
an
assay
using
spheroids
with
fluorescently
tagged
apical
surfaces,
allowing
us
visualize
quantify
tubule–tubule
connections.
results
demonstrate
that
HGF
promotes
anastomosis,
it
does
so
through
MAPK
signaling
pathway
MMPs,
independently
cell
proliferation.
Remarkably,
treatment
collagenase
was
sufficient
induce
anastomosis
in
kidneys.
These
findings
provide
foundational
understanding
how
enhance
tubular
networks.
This
has
significant
clinical
implications
use
vitro–grown
tissues
transplant
medicine,
potentially
improving
success
integration
transplanted
tissues.
Biomedicines,
Год журнала:
2025,
Номер
13(2), С. 523 - 523
Опубликована: Фев. 19, 2025
Autosomal
dominant
polycystic
kidney
disease
(ADPKD)
is
a
prevalent
hereditary
disorder
characterized
by
distinct
phenotypic
variability
that
has
posed
challenges
for
advancing
in-depth
research.
Recent
advancements
in
organoid
construction
technologies
have
enabled
researchers
to
simulate
development
and
create
simplified
vitro
experimental
environments,
allowing
more
direct
observation
of
how
genetic
mutations
drive
pathological
phenotypes
disrupt
physiological
functions.
Emerging
technologies,
such
as
microfluidic
bioreactor
culture
systems
single-cell
transcriptomics,
further
supported
the
complex
ADPKD
organoids,
offering
robust
models
exploring
mechanisms
facilitating
drug
discovery.
Nevertheless,
significant
remain
constructing
accurate
models.
This
review
will
summarize
recent
advances
construction,
focusing
on
limitations
current
techniques
critical
issues
need
be
addressed
future
breakthroughs.
New
Noteworthy:
presents
particularly
iPSC-derived
models,
new
insights
into
It
focuses
limited
vascularization
maturity,
proposing
potential
solutions
through
emerging
technologies.
The
ongoing
optimization
expected
enhance
understanding
breakthroughs
targeted
therapy
development.
Cells,
Год журнала:
2024,
Номер
13(14), С. 1190 - 1190
Опубликована: Июль 13, 2024
Genetic
or
hereditary
kidney
disease
stands
as
a
pivotal
cause
of
chronic
(CKD).
The
proliferation
and
widespread
utilization
DNA
testing
in
clinical
settings
have
notably
eased
the
diagnosis
genetic
diseases,
which
were
once
elusive
but
are
now
increasingly
identified
cases
previously
deemed
CKD
unknown
etiology.
However,
despite
these
diagnostic
strides,
research
into
pathogenesis
novel
drug
development
faces
significant
hurdles,
chiefly
due
to
dearth
appropriate
animal
models
challenges
posed
by
limited
patient
cohorts
studies.
Conversely,
advent
human-induced
pluripotent
stem
cells
(hiPSCs)
offer
promising
avenue
for
research.
Particularly,
hiPSC-derived
organoid
systems
presents
platform
investigating
various
forms
diseases.
Moreover,
integration
CRISPR/Cas9
technique
this
system
holds
immense
potential
efficient
on
This
review
aims
explore
applications
vitro
organoids
generated
from
hiPSCs
study
diverse
Additionally,
it
will
delve
limitations
outline
future
perspectives
advancing
crucial
area.
Chinese Medical Journal,
Год журнала:
2025,
Номер
unknown
Опубликована: Фев. 25, 2025
Abstract
The
high
failure
rates
in
clinical
drug
development
based
on
animal
models
highlight
the
urgent
need
for
more
representative
human
biomedical
research.
In
response
to
this
demand,
organoids
and
organ
chips
were
integrated
greater
physiological
relevance
dynamic,
controlled
experimental
conditions.
This
innovative
platform—the
organoids-on-a-chip
technology—shows
great
promise
disease
modeling,
discovery,
personalized
medicine,
attracting
interest
from
researchers,
clinicians,
regulatory
authorities,
industry
stakeholders.
review
traces
evolution
organoids-on-a-chip,
driven
by
necessity
advanced
biological
models.
We
summarize
applications
of
simulating
pathological
phenotypes
therapeutic
evaluation
technology.
section
highlights
how
integrating
technologies
chips,
such
as
microfluidic
systems,
mechanical
stimulation,
sensor
integration,
optimizes
organoid
cell
types,
spatial
structure,
functions,
thereby
expanding
their
applications.
conclude
addressing
current
challenges
offering
insights
into
prospects.
advancement
is
poised
enhance
fidelity,
standardization,
scalability.
Furthermore,
integration
cutting-edge
interdisciplinary
collaborations
will
be
crucial
progression
Abstract
Tissue
regeneration
has
raised
intensive
attention
due
to
its
great
significance
in
overcoming
various
diseases
resulting
from
different
injuries.
Since
the
COVID‐19
pandemic,
mRNA
therapeutics
have
emerged
as
innovative
strategies
prevention
and
treatment
of
their
unique
advantages.
Compared
traditional
regenerative
strategies,
therapy
offers
rapid
translation
into
proteins
with
low
production
cost
high
modifiability.
Herein,
we
discuss
progress
key
processes
therapy,
focusing
on
therapeutic
modification
delivery
carriers.
The
preclinical
clinical
studies
for
cardiac,
lung,
liver,
kidney,
locomotor
system,
skin
lesions
neurological
disorders
were
summarized
comprehensively.
Developing
reduce
immunogenicity
off‐target
effects,
well
optimization
system
may
accelerate
pace
translation.
ABSTRACT
In
the
developing
mammalian
kidney,
nephron
formation
is
initiated
by
a
subset
of
progenitor
cells
(NPCs).
Wnt
input
activates
β-catenin
(Ctnnb1)-driven,
transcriptional
nephrogenic
program
and
mesenchymal
to
epithelial
transition
(MET)
NPCs.
Using
an
in
vitro
mouse
NPC
culture
model,
we
observed
that
activation
pathway
results
aggregation
induced
NPCs,
which
initiating
step
MET
program.
Genetic
removal
showed
was
dependent
on
β-catenin.
Modulating
extracellular
Ca2+
levels
cell-cell
contacts
were
dependent,
suggesting
role
for
cadherin
(Cdh)-directed
cell
adhesion.
Molecular
analysis
identified
Cdh2,
Cdh4
Cdh11
directed
upregulation
Cdh3
accompanying
Mutational
supported
Lef/Tcf-β-catenin-mediated
response
process.
all
four
cadherins,
independent
α-catenin
or
β-catenin-α-catenin
interactions,
abolished
aggregation,
but
not
inductive
activation.
These
findings,
data
article
highlight
linking
programs
morphogenesis
NPCs
nephrogenesis.
