4697281_monash_120601.pdf (11.8 MB)
Therapeutic effects of human amniotic epithelial cells in a murine model of multiple sclerosis
thesis
posted on 2017-05-18, 04:43 authored by Liu, Yu-HanMultiple sclerosis (MS) is an inflammatory demyelinating disease that has 1/1000
prevalence in the Western world. Current therapies for MS are only partially effective
and are accompanied by undesirable side effects. In this thesis I examined a newly
emerged placental-derived cell, amniotic epithelial cell (hAEC), as cell therapy for a
myelin oligodendrocyte glycoprotein (MOG) peptide-induced MS model of
experimental autoimmune encephalomyelitis (EAE). I tested the effects of hAEC in
preventing or intervening EAE disease course. In both instances I found milder
neurological signs, reduced inflammation in the spinal cord accompanied by lowered
peripheral immune responses against MOG peptide. In searching for mechanisms by
which hAEC mediate their therapeutic roles, I found that hAEC inhibited
antigen-nonspecific and antigen-specific splenocyte proliferation in a dose-dependent
manner. Transforming growth factor-β (TGF-β) and prostaglandin E2 (PGE2) are
essential for this suppression in vitro. Because MS is thought to be a T cell-mediated
disease, the ability to modulate T cell response is key to control MS progression. I
found that splenic T cells from hAEC-treated EAE mice showed elevated IL-5
production, and in the intervention model there was also elevated production of IL-2
and IL-5. Peripheral immune cell populations in spleens and lymph nodes were mainly
unchanged except for elevated regulatory T cells found in the intervention model after
corticosteroid-induced remission followed by hAEC treatment. There were also
decreased secretions of MOG-specific antibodies in sera of mice in both the prevention
and intervention models, reflecting the alleviated peripheral autoimmune responses
after hAEC treatment. hAEC were found in the lung but not other organs after
intravenous delivery to EAE mice. My data suggest that hAEC may have potential as
cell therapy for MS to prevent and to alleviate relapse of MS. Compared to primary
hAEC, expanded hAEC in culture showed morphological changes, reduced
suppressive capacity and lower production of immunomodulatory molecules.
hAEC-derived hepatocyte-like cells exhibit immunogenicity, which is not evident in
primary hAEC, but still retain immunomodulatory properties via secreted factors.
These findings suggest that hAEC may also be applied as cell therapy for
organ-specific diseases and tissue transplantation.
History
Principal supervisor
Ban-Hock TohYear of Award
2014Department, School or Centre
Inflammatory DiseasesAdditional Institution or Organisation
Monash Medical CentreCampus location
AustraliaCourse
Doctor of PhilosophyDegree Type
DOCTORATEFaculty
Faculty of Medicine Nursing and Health SciencesUsage metrics
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