Transforming the Niche: The Emerging Role of Extracellular Vesicles in Acute Myeloid Leukaemia Progression
International Journal of Molecular Sciences,
Год журнала:
2024,
Номер
25(8), С. 4430 - 4430
Опубликована: Апрель 17, 2024
Acute
myeloid
leukaemia
(AML)
management
remains
a
significant
challenge
in
oncology
due
to
its
low
survival
rates
and
high
post-treatment
relapse
rates,
mainly
attributed
treatment-resistant
leukaemic
stem
cells
(LSCs)
residing
bone
marrow
(BM)
niches.
This
review
offers
an
in-depth
analysis
of
AML
progression,
highlighting
the
pivotal
role
extracellular
vesicles
(EVs)
dynamic
remodelling
BM
niche
intercellular
communication.
We
explore
recent
advancements
elucidating
mechanisms
through
which
EVs
facilitate
complex
crosstalk,
effectively
promoting
hallmarks
drug
resistance.
Adopting
temporal
view,
we
chart
evolving
landscape
EV-mediated
interactions
within
niche,
underscoring
transformative
potential
these
insights
for
therapeutic
intervention.
Furthermore,
discusses
emerging
understanding
endothelial
cell
subsets'
impact
across
niches
shaping
disease
adding
another
layer
complexity
progression
treatment
highlight
cutting-edge
methodologies,
such
as
organ-on-chip
(OoC)
single-EV
technologies,
provide
unprecedented
into
AML-niche
human
setting.
Leveraging
accumulated
EV
signalling
reconfigure
pioneer
novel
approaches
decipher
networks
that
fuel
context
could
revolutionise
development
niche-targeted
therapy
eradication.
Язык: Английский
Special issue: Recent advances in immunotherapy and immunoengineering
Bioactive Materials,
Год журнала:
2025,
Номер
48, С. 529 - 530
Опубликована: Фев. 28, 2025
Язык: Английский
High throughput morphological screening identifies chemically defined media for mesenchymal stromal cells that enhances proliferation and supports maintenance of immunomodulatory function
Thomas M. Spoerer,
Andrew M. Larey,
Winifred Asigri
и другие.
Stem Cell Research & Therapy,
Год журнала:
2025,
Номер
16(1)
Опубликована: Март 7, 2025
Abstract
Background
While
mesenchymal
stromal
cell
(MSC)
therapies
show
promise
for
treating
several
indications
due
to
their
regenerative
and
immunomodulatory
capacity,
clinical
translation
has
yet
be
achieved
a
lack
of
robust,
scalable
manufacturing
practices.
Expansion
using
undefined
fetal
bovine
serum
(FBS)
or
human
platelet
lysate
contributes
MSC
functional
heterogeneity
limits
control
product
quality.
The
need
tunable
consistent
media
thus
motivated
development
chemically
defined
(CDM).
However,
CDM
strategies
are
often
limited
in
screening
approaches
unable
reliably
assess
the
impact
on
function,
neglecting
high-level
interactions
components
such
as
growth
factors.
Given
that
morphology
been
shown
predict
we
employed
high
throughput
(HTS)
approach
elucidate
effects
factor
compositions
phenotype
proliferation
custom
CDM.
Methods
HTS
eight
factors
basal
medium
(CDBM)
was
conducted
via
two-level,
full
factorial
design
adipose-derived
MSCs.
Media
hits
were
identified
leveraging
counts
morphological
profiles.
After
validating
phenotypic
responses
across
multiple
donors,
MSCs
cultured
over
three
passages
serum-containing
(SCM)
assayed
function.
Finally,
concentrations
one
hit
further
refined,
function
assessed.
Results
Our
led
discovery
formulations
enhanced
demonstrated
wide
ranging
impacts
immunomodulation.
Notably,
two
showed
4X
higher
compared
SCM
3
without
compromising
Refinement
formulation
reduced
by
much
90%
while
maintaining
superior
similar
SCM.
Altogether,
distinct
profiles
observed
from
indicative
differential
quality
allowed
an
effective
expansion.
Conclusions
Overall,
this
highlights
how
our
robust
expansion
serves
generalizable
tool
improvement
processes.
Язык: Английский
Effects of Hydrogels on Mesenchymal Stem/Stromal Cells Paracrine Activity and Extracellular Vesicles Production
Journal of Extracellular Vesicles,
Год журнала:
2025,
Номер
14(3)
Опубликована: Март 1, 2025
ABSTRACT
Mesenchymal
stem/stromal
cells
(MSCs)
are
a
valuable
source
of
paracrine
factors,
as
they
have
remarkable
secretory
capacity,
and
there
is
sizeable
knowledge
base
to
develop
industrial
clinical
production
protocols.
Promising
cell‐free
approaches
for
tissue
regeneration
immunomodulation
driving
research
towards
secretome
applications,
among
which
extracellular
vesicles
(EVs)
steadily
gaining
attention.
However,
the
manufacturing
application
EVs
limited
by
insufficient
yields,
gaps,
low
standardization.
Facing
these
limitations,
hydrogels
represent
versatile
three‐dimensional
(3D)
culture
platform
that
can
incorporate
matrix
(ECM)
components
mimic
natural
stem
cell
environment
in
vitro;
via
niche‐mimicking
properties,
regulate
MSCs’
morphology,
adhesion,
proliferation,
differentiation
secretion
capacities.
impact
hydrogel's
architectural,
biochemical
biomechanical
properties
on
remains
poorly
understood,
field
still
its
infancy
interdependency
parameters
compromises
comparability
studies.
Therefore,
this
review
summarizes
discusses
reported
effects
hydrogel
encapsulation
MSC‐EVs.
Considering
cell‐material
interactions
overall
activity
MSCs,
we
identify
persistent
challenges
from
standardization
process
control,
outline
future
paths
research,
such
synergic
use
bioreactors
enhance
MSC‐EV
generation.
Язык: Английский
Mesenchymal Stem Extracellular Vesicles in Various Respiratory Diseases: A New Opportunity
Journal of Inflammation Research,
Год журнала:
2024,
Номер
Volume 17, С. 9041 - 9058
Опубликована: Ноя. 1, 2024
Lung
diseases
are
associated
with
high
morbidity
and
mortality
rates,
thereby
jeopardizing
human
health
imposing
a
great
burden
on
society.
Currently,
lung
mainly
treated
medications,
oxygen
therapy
mechanical
ventilation,
but
these
approaches
unable
to
effectively
reduce
the
rate.
Therefore,
transplantation
remains
ultimate
treatment
for
various
chronic
diseases,
this
is
also
hindered
by
limited
availability
of
sources,
immature
technology
low
survival
rate
after
transplantation.
With
constant
changes
in
environment,
pathogens,
type
amount
harmful
substances
prevalence
respiratory
there
an
urgent
need
identify
alternative
methods.
Research
stem
cell
has
been
very
successful
recent
years,
mesenchymal
cells
(MSCs),
together
their
secretory
bodies,
play
significant
therapeutic
role.
Extracellular
vesicles
MSCs
(MSC-EVs)
major
components
paracrine
secretion
MSCs,
including
exosomes,
microvesicles,
apoptotic
among
which
exosomes
most
typical.
MSC-EVs
believed
be
present
tissues
body
where
they
can
carry
proteins,
DNA,
RNA
biologically
active
factors,
just
name
few.
They
transmit
biological
signals
participate
different
activities,
maintenance
homeostasis
within
tissue.
Several
studies
have
further
demonstrated
that
generated
extracellular
important
role
diseases.
In
paper,
origin,
properties
roles
reviewed,
mechanisms
limitations
current
options
Chronic
Obstructive
Pulmonary
Disease,
asthma,
infectious
disease,
cancer,
pulmonary
fibrosis,
arterial
hypertension,
acute
injury/
distress
syndrome
discussed
(Figure
1).
addition,
possible
future
research
directions
view
providing
new
ideas
Язык: Английский
Microglia Morphological Response to Mesenchymal Stromal Cell Extracellular Vesicles Demonstrates EV Therapeutic Potential for Modulating Neuroinflammation
Kanupriya R. Daga,
Andrew M. Larey,
Maria G. Morfin
и другие.
bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2024,
Номер
unknown
Опубликована: Июль 3, 2024
ABSTRACT
Background
Mesenchymal
stromal
cell
derived
extracellular
vesicles
(MSC-EVs)
are
a
promising
therapeutic
for
neuroinflammation.
MSC-EVs
can
interact
with
microglia,
the
resident
immune
cells
of
brain,
to
exert
their
immunomodulatory
effects.
In
response
inflammatory
cues,
such
as
cytokines,
microglia
undergo
phenotypic
changes
indicative
function
e.g.
morphology
and
secretion.
However,
these
in
not
well
understood.
Additionally,
no
disease-relevant
screening
tools
assess
MSC-EV
bioactivity
exist,
which
has
further
impeded
clinical
translation.
Here,
we
developed
quantitative,
high
throughput
morphological
profiling
approach
neuroinflammation-relevant
signals
whether
this
be
used
indicate
MSC-EVs.
Results
Using
an
immortalized
human
cell-line,
observed
increased
size
(perimeter,
major
axis
length)
complexity
(form
factor)
upon
stimulation
interferon-gamma
(IFN-γ)
tumor
necrosis
factor-alpha
(TNF-α).
Upon
treatment
MSC-EVs,
overall
score
(determined
using
principal
component
analysis)
shifted
towards
unstimulated
morphology,
indicating
that
bioactive
modulate
microglia.
The
effects
TNF-γ/IFN-α
stimulated
were
concomitant
reduced
secretion
14
chemokines/cytokines
(e.g.
CXCL6,
CXCL9)
12
CXCL8,
CXCL10).
Proteomic
analysis
lysates
revealed
significant
increases
192
proteins
HIBADH,
MEAK7,
LAMC1)
decreases
257
PTEN,
TOM1,
MFF)
treatment.
Of
note,
many
involved
regulation
migration.
Gene
Set
Variation
Analysis
upregulation
pathways
associated
response,
cytokine
production,
infiltration
T
cells,
NK
cells)
Semaphorin,
RHO/Rac
signaling).
mitochondrial
measured
suggesting
metabolism.
Conclusion
This
study
comprehensively
demonstrates
on
microglial
secretion,
cellular
proteome,
content.
Our
high-throughput,
rapid,
low-cost
enables
batches
manufacturing
conditions
enhance
EV
mitigate
functional
heterogeneity
disease
relevant
manner.
is
highly
generalizable
adapted
refined
based
selection
signal,
target
cell,
product.
Язык: Английский
Microglia morphological response to mesenchymal stromal cell extracellular vesicles demonstrates EV therapeutic potential for modulating neuroinflammation
Kanupriya R. Daga,
Andrew M. Larey,
Maria G. Morfin
и другие.
Journal of Biological Engineering,
Год журнала:
2024,
Номер
18(1)
Опубликована: Окт. 17, 2024
Mesenchymal
stromal
cell
derived
extracellular
vesicles
(MSC-EVs)
are
a
promising
therapeutic
for
neuroinflammation.
MSC-EVs
can
interact
with
microglia,
the
resident
immune
cells
of
brain,
to
exert
their
immunomodulatory
effects.
In
response
inflammatory
cues,
such
as
cytokines,
microglia
undergo
phenotypic
changes
indicative
function
e.g.
morphology
and
secretion.
However,
these
in
not
well
understood.
Additionally,
no
disease-relevant
screening
tools
assess
MSC-EV
bioactivity
exist,
which
has
further
impeded
clinical
translation.
Here,
we
developed
quantitative,
high
throughput
morphological
profiling
approach
neuroinflammation-
relevant
signals
whether
this
be
used
indicate
MSC-EVs.
Язык: Английский