Page 76 - Mesenchymal Stem Cell-Derived Exosomes as an Emerging Paradigm for Regenerative Therapy and Nano-Medicine

C. R. Harrell et al.

indicating their therapeutic potential in the mediated diseases and promote regeneration of
treatment of Mucopolysaccharidosis VII (Sly ischemic tissues in almost completely the same
Syndrome). Importantly, beneficent effects way as transplanted MSCs indicating that para-
were noticed only in animals that received crine mechanisms are mainly responsible for
MSC-derived exosomes and were not seen MSC-based therapeutic effects and that therapeu-
after therapy with fibroblasts-derived tic use of MSC-derived products may overcome
exosomes confirming specific therapeutic safety concerns regarding unwanted differentia-
potential of MSCs and their products in the tion of transplanted MSCs (Volarevic et al. 2017,
treatment of eye diseases. 2018).
In conclusion, MSC-derived exosomes rep- Since it was recently revealed that exosomes
resent potentially new therapeutic agents in the play an important role in biological functions of
therapy of degenerative and inflammatory ocu- MSCs and MSC-CM (Yu et al. 2014; Rani et al.
lar diseases. 2015; Lai et al. 2015), herewith we summarized
current knowledge about the morphology, struc-
Keywords ture, phenotype and functional characteristics of
Mesenchymal stem cells · Exosomes · Eye · MSC-derived exosomes emphasizing their thera-
Injury · Inflammation peutic potential in the treatment of eye diseases.
An extensive literature review was carried out in
April 2018 across several databases (MEDLINE,
EMBASE, Google Scholar), from 1990 to pres-
1 Introduction
ent. Keywords used in the selection were: “mes-
enchymal stem cells”, “exosomes”, “eye”,
Due to their capacity to produce trophic and
“degenerative diseases”, “inflammatory
immunosuppressive factors, mesenchymal stem
diseases”, “regeneration”, “immunosuppression”.
cells [MSCs] were extensively explored as new
Studies that emphasized molecular and cellular
therapeutic agents in cell-based therapy of uveitis,
mechanisms responsible for beneficent effects of
glaucoma, retinal and ocular surface diseases (Joe
MSC-derived exosomes in the therapy of eye
and Gregory-Evans 2010). Although obtained
diseases were analyzed in this review.
results were promising, safety issues regarding
MSCs-based transplantation are still a matter of
debate, especially in the long-term follow up. The
2 MSC Derived Exosomes:
primary concern is unwanted differentiation of Morphology and Structure
the transplanted MSCs induced by cellular and
cytokine milieu of local microenvironment in
MSC-derived exosomes are nano-sized extracellu-
which MSCs were engrafted (Volarevic et al.
lar vesicles that originate via the inward budding of
2018). It was recently reported that three women
the late endosome membranes called multivesicular
suffering from macular degeneration developed
bodies (MVBs). Upon the fusion of MVBs with the
complications including vision loss, detached
plasma membrane, MSC-derived exosomes are
retinas, and bleeding resulting in total blindness
released into the extracellular milieu and can be
in stem cell-treated eyes as a consequence of
either taken up by target cells residing in the micro-
unwanted differentiation of transplanted stem
environment of engrafted MSCs or may be carried
cells (Kuriyan et al. 2017).
to distant sites via biological fluids where, in endo-
As far as we know to date, beneficial effects of
crine manner, modulate function of immune cells,
MSCs in cell-based therapy of degenerative and
endothelial cells (ECs), pericytes and other tissue-
autoimmune disease are largely due to the activity
resident cells (Hyenne et al. 2015)
of MSC-derived trophic and immunosuppressive
MSC derived exosomes have a narrow diameter
soluble factors (Volarevic et al. 2017). Plenty of
range of 40–100 nm and a density of
evidence indicate that MSCs conditioned medium 1
1.13–1.19 gml in sucrose solution. Their
(MSC-CM) attenuate progression of immune
membranes are enriched in cholesterol