Kennelly, Helen (2015) Investigation of efficacy and mechanisms of action in mesenchymal stromal cell therapy for chronic lung diseases. PhD thesis, National University of Ireland Maynooth.
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Abstract
Mesenchymal
Stromal
Cells
(MSC)
are
adult
multipotent
cells
that
possess
self-‐renewal
and
regenerative
capacities,
with
the
ability
to
differentiate
into
a
variety
of
cell
types.
They
have
potent
immunosuppressive
abilities,
facilitating
the
use
of
allogeneic
MSC
as
a
cellular
therapy.
Functionally,
it
is
the
trophic
mediated
effects
of
MSC
that
have
become
the
focus
of
research
due
to
paracrine
mediated
tissue
reparative
and
protective
effects.
This
study
has
examined
the
use
of
MSC
for
the
treatment
of
inflammatory
and
fibrotic
lung
diseases,
specifically
Chronic
Obstructive
Pulmonary
Disease
(COPD)
and
Idiopathic
Pulmonary
Fibrosis
(IPF).
In
vitro
characterisation
of
MSC
demonstrated
significant
cytoprotective
and
reparative
effects,
through
inhibition
of
epithelial
apoptosis,
suppression
of
neutrophil
functions
and
repair
of
injured
epithelial
cells.
These
effects
were
mediated
by
MSC
production
of
HGF
and
subsequent
paracrine
signalling.
Utilising
a
humanised
mouse
model
of
COPD,
MSC
administration
resulted
in
beneficial
cytoprotective
effects
due
to
HGF,
including
reduced
inflammation,
and
epithelial
apoptosis.
These
effects
were
greatest
with
early
MSC
administration
with
reduced
efficacy
following
late
MSC
administration.
In
a
bleomycin
mouse
model
of
fibrosis,
MSC
again
displayed
significant
cytoprotective
effects
with
early
MSC
intervention.
Decreased
epithelial
apoptosis
and
collagen
deposition
were
observed
with
MSC
treatment
with
HGF
demonstrated
to
be
important
in
this
process.
The
work
presented
here
demonstrates
significant
protective
effects
of
early
MSC
treatment
in
inflammatory
and
fibrotic
lung
diseases
mediated
in
part
by
MSC
production
of
HGF.
Item Type: | Thesis (PhD) |
---|---|
Keywords: | Investigation; efficacy; mechanisms; action; mesenchymal stromal cell therapy; chronic lung diseases; |
Academic Unit: | Faculty of Science and Engineering > Biology Faculty of Science and Engineering > Research Institutes > Institute of Immunology |
Item ID: | 10372 |
Depositing User: | IR eTheses |
Date Deposited: | 04 Jan 2019 16:23 |
URI: | https://mural.maynoothuniversity.ie/id/eprint/10372 |
Use Licence: | This item is available under a Creative Commons Attribution Non Commercial Share Alike Licence (CC BY-NC-SA). Details of this licence are available here |
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