Journal of Neuro-Oncology,
Год журнала:
2024,
Номер
169(2), С. 329 - 340
Опубликована: Июнь 20, 2024
Abstract
Purpose
Mesenchymal
stromal
cells
(MSCs)
within
the
glioblastoma
microenvironment
have
been
shown
to
promote
tumor
progression.
Tumor
Treating
Fields
(TTFields)
are
alternating
electric
fields
with
low
intensity
and
intermediate
frequency
that
exhibit
anti-tumorigenic
effects.
While
effects
of
TTFields
on
studied
previously,
nothing
is
known
about
influence
MSCs.
Methods
Single-cell
RNA
sequencing
immunofluorescence
staining
were
employed
identify
glioblastoma-associated
MSCs
in
patient
samples.
Proliferation
clonogenic
survival
human
bone
marrow-derived
assessed
after
vitro.
MSC’
characteristic
surface
marker
expression
was
determined
using
flow
cytometry,
while
multi-lineage
differentiation
potential
examined
immunohistochemistry.
Apoptosis
quantified
based
caspase-3
annexin-V/7-AAD
levels
senescence
ß-galactosidase
staining.
MSCs’
migratory
evaluated
Boyden
chamber
assays.
Results
showed
presence
significantly
reduced
proliferation
by
up
60%
90%,
respectively.
capacity
intact
TTFields,
treatment
resulted
increased
apoptosis
senescence.
Furthermore,
capacity.
Conclusion
We
could
demonstrate
tumor-associated
patients,
providing
a
rationale
study
impact
considerably
increase
MSCs,
resulting
impaired
migration.
The
results
provide
basis
for
further
analyses
role
patients
receiving
TTFields.
Abstract
Horizontal
transfer
of
mitochondria
from
the
tumour
microenvironment
to
cancer
cells
support
proliferation
and
enhance
progression
has
been
shown
for
various
types
in
recent
years.
Glioblastoma,
most
aggressive
adult
brain
tumour,
proven
be
no
exception
when
it
comes
dynamic
intercellular
mitochondrial
movement,
as
this
study
using
an
orthotopic
model
respiration-deficient
glioblastoma
cells.
Although
confirmed
was
facilitate
glioblastoma,
we
decided
investigate
whether
related
electron
transport
chain
recovery
is
necessary
formation
brain.
Based
on
experiments
time-resolved
analysis
by
depleted
their
DNA,
conclude
that
functional
respiration
essential
growth
vivo,
because
needed
coenzyme
Q
redox
cycling
de
novo
pyrimidine
biosynthesis
controlled
respiration-linked
dihydroorotate
dehydrogenase
enzyme
activity.
We
also
demonstrate
here
astrocytes
are
key
donors
model.
The
role
of
mesenchymal
stem
cells
(MSCs)
in
the
breast
tumor
microenvironment
(TME)
is
significant
and
multifaceted.
MSCs
are
recruited
to
sites
through
molecular
signals
released
by
sites.
Once
TME,
undergo
polarization
interact
with
various
cell
populations,
including
immune
cells,
cancer-associated
fibroblasts
(CAFs),
cancer
(CSCs),
cells.
In
most
cases,
play
roles
therapeutic
resistance,
but
there
also
evidence
that
indicates
their
abilities
sensitize
chemotherapy
radiotherapy.
possess
inherent
regenerative
homing
properties,
making
them
attractive
candidates
for
cell-based
therapies.
Therefore,
can
be
engineered
express
molecules
or
deliver
anti-cancer
agents
directly
Unraveling
intricate
relationship
between
TME
has
potential
uncover
novel
targets
advance
our
understanding
biology.
Brain Sciences,
Год журнала:
2024,
Номер
14(9), С. 899 - 899
Опубликована: Сен. 5, 2024
The
role
of
mitochondria
in
neurodegenerative
diseases
is
crucial,
and
recent
developments
have
highlighted
its
significance
cell
therapy.
Mitochondrial
dysfunction
has
been
implicated
various
disorders,
including
Alzheimer's,
Parkinson's,
amyotrophic
lateral
sclerosis,
Huntington's
diseases.
Understanding
the
impact
mitochondrial
biology
on
these
conditions
can
provide
valuable
insights
for
developing
targeted
therapies.
This
mini-review
refocuses
emphasizes
potential
therapies
leveraging
mesenchymal
stem
cells,
embryonic
induced
pluripotent
cell-derived
secretions,
extracellular
vesicles.
Mesenchymal
cell-mediated
transfer
restoring
health
cells
with
dysfunctional
mitochondria.
Additionally,
attention
paid
to
gene-editing
techniques
such
as
mito-CRISPR,
mitoTALENs,
mito-ZNFs,
DdCBEs
ensure
safety
efficacy
treatments.
Challenges
future
directions
are
also
discussed,
possible
tumorigenic
effects
off-target
effects,
disease
targeting,
immune
rejection,
ethical
issues.
Frontiers in Oncology,
Год журнала:
2024,
Номер
14
Опубликована: Янв. 26, 2024
Background
Tumor
heterogeneity
is
one
of
the
key
factors
leading
to
chemo-resistance
relapse.
It
remains
unknown
how
resistant
cancer
cells
influence
sensitive
during
cohabitation
and
growth
within
a
heterogenous
tumors.
The
goal
our
study
was
identify
driving
that
mediate
interactions
between
determine
effects
on
both
phenotypes.
Methods
We
used
isogenic
ovarian
(OC)
cell
lines
pairs,
platinum:
OVCAR5
vs.
CisR
PE01
PE04,
respectively,
perform
long
term
direct
culture
phenotypical
changes
interaction
these
cells.
Results
Long
co-culture
OC
promoted
proliferation
(p
<
0.001)
increased
proportion
in
G1
S
cycle
phase
Direct
led
decrease
IC50
platinum
cisplatin-sensitive
(5.92
µM
2.79
for
PE01,
from
2.05
1.51
OVCAR5).
RNAseq
analysis
co-cultured
showed
enrichment
Cell
Cycle
Control,
Cyclins
Regulation
pathways.
transcription
factor
E2F1
predicted
as
main
effector
responsible
transcriptomic
Western
blot
qRT-PCR
confirmed
upregulation
vs
monoculture.
Furthermore,
an
inhibitor
reverted
increase
rate
induced
by
baseline
levels.
Conclusion
Our
data
suggest
chemo-sensitive
-resistant
drive
higher
proliferative
state,
more
responsive
platinum.
results
reveal
unexpected
effect
caused
with
different
rates
levels
resistance,
modelling
competition
heterogeneous
Journal of Neuro-Oncology,
Год журнала:
2024,
Номер
169(2), С. 329 - 340
Опубликована: Июнь 20, 2024
Abstract
Purpose
Mesenchymal
stromal
cells
(MSCs)
within
the
glioblastoma
microenvironment
have
been
shown
to
promote
tumor
progression.
Tumor
Treating
Fields
(TTFields)
are
alternating
electric
fields
with
low
intensity
and
intermediate
frequency
that
exhibit
anti-tumorigenic
effects.
While
effects
of
TTFields
on
studied
previously,
nothing
is
known
about
influence
MSCs.
Methods
Single-cell
RNA
sequencing
immunofluorescence
staining
were
employed
identify
glioblastoma-associated
MSCs
in
patient
samples.
Proliferation
clonogenic
survival
human
bone
marrow-derived
assessed
after
vitro.
MSC’
characteristic
surface
marker
expression
was
determined
using
flow
cytometry,
while
multi-lineage
differentiation
potential
examined
immunohistochemistry.
Apoptosis
quantified
based
caspase-3
annexin-V/7-AAD
levels
senescence
ß-galactosidase
staining.
MSCs’
migratory
evaluated
Boyden
chamber
assays.
Results
showed
presence
significantly
reduced
proliferation
by
up
60%
90%,
respectively.
capacity
intact
TTFields,
treatment
resulted
increased
apoptosis
senescence.
Furthermore,
capacity.
Conclusion
We
could
demonstrate
tumor-associated
patients,
providing
a
rationale
study
impact
considerably
increase
MSCs,
resulting
impaired
migration.
The
results
provide
basis
for
further
analyses
role
patients
receiving
TTFields.
