Page 80 - Mesenchymal Stem Cell-Derived Exosomes as an Emerging Paradigm for Regenerative Therapy and Nano-Medicine

C. R. Harrell et al.

2017). In line with these observations, our pre- macrophages and attenuate consequent apoptosis
liminary results showed that AF-MSC-derived of retinal cells when compared to vehicle-treated
ophthalmic solution, which contains a high con- group. MSC-derived exosomes managed to sig-
centration of immunosuppressive GRO and IDO, nificantly alleviate expression of inflammatory
significantly attenuated dryness, grittiness, mediators in the injured retinas involved in migra-
scratchiness, soreness, irritation, burning, tion of monocytes in the eye: cytokine (TNF-α),
watering, and eye fatigue in patients suffering chemokine (monocyte chemoattractant protein-1,
from DED, indicating therapeutic potential of MCP-1) and adhesion molecule (intercellular
AF-MSC-derived secretomes in the treatment Adhesion Molecule 1, ICAM-1). Application of
of DED. MCP-1 abolished effects of MSC-derived
exosomes suggesting that they reduce retinal
injury and inflammation mainly by targeting
MCP-1-dependent migration of monocytes
4 MSC Derived Exosomes
(Yu et al. 2016). In accordance to the attenuated
in the Therapy of Retinal Injury
retinal injury and inflammation, the significant
improvement of dark- and light-adapted electro-
Damage of retinal cells caused by injury, infec-
retinogram response in laser-injured mice treated
tion or ischemia triggers degeneration in neigh-
with MSC-derived exosomes was observed,
boring neural cells, resulting with the spread of
indicating functional recovery of retinal cells
morphological and functional retinal damage and
(Yu et al. 2016).
irreversible visual impairment (Yoles and
In line with result obtained by Yu and
Schwartz 1998). Till now, there is no effective
colleagues (Yu et al. 2016) are findings recently
neuroprotection therapy currently available for
reported by Mead and Tomarev (Mead and
retinal injury and, accordingly, transplantation of
Tomarev 2017) who demonstrated therapeutic
stem cells and their products have been exten-
potential of bone marrow MSCs [BM-MSCs]-
sively tested as new therapeutic approach for
derived exosomes in the regeneration of injured
retinal regeneration. By using animal model of
retinal ganglion cells [RGCs]. RGCs are the sole
laser-induced retinal injury, Yu and coworkers
projection neurons and their axons make up the
recently demonstrated therapeutic potential of
optic nerve, making them susceptible to traumatic
MSC-derived exosomes in attenuation of retinal
(optic nerve crush; ONC) and degenerative (glau-
damage and inflammation (Fig. 2) (Yu et al.
coma) diseases. Since RGC are CNS neurons,
2016). One hour after their intravitreal injection,
they are neither replaceable nor capable of axon
MSC-derived exosomes diffused rapidly through-
regeneration and their loss or dysfunction results
out the neural retina, retinal pigment epithelium
with irreversible blindness. BM-MSC-derived
and gradually spread to the outer layers. Impor-
exosomes efficiently promoted survival and
tantly, MSC-derived exosomes were as efficient
neuritogenesis of RGCs in vitro and in vivo,in
as transplanted MSCs in limiting the extent of
ONC experimental model. In compared to
retinal damage. MSC-exosome-treated and
untreated animals where, 3 weeks after ONC,
MSC-treated eyes showed equivalent attenuation
more than 80% of RGCs are lost, cell death of
of laser-induced retinal injury with milder disor-
RGCs was reduced to 30% in rats treated with
ganization of the tissue, more residual photore-
BM-MSC-derived exosomes. Moreover, in
ceptor cells, smaller retinal disordered areas, and
BM-MSC exosome-treated retinas, over 50% of
reduced loss of nuclei in the outer nuclear layers
RGC function was maintained, suggesting that
compared with the eyes that were treated with
exosomes managed not only to protect RGC
vehicle only. Furthermore, application of
from death but also to preserve their function.
MSC-derived exosomes significantly reduced
Importantly, this was significantly higher
infiltration of immune cells, particularly CD68+