Page 83 - Mesenchymal Stem Cell-Derived Exosomes as an Emerging Paradigm for Regenerative Therapy and Nano-Medicine

Therapeutic Potential of Mesenchymal Stem Cell-Derived Exosomes in the.. .

6 Effects of MSC-Derived 7 Conclusion
Exosomes in the Treatment
of Sly Syndrome Although transplantation of MSCs has enormous
perspective in regenerative medicine,
Mucopolysaccharidosis (MPS) is a group of seven accumulating evidence indicates that treatment
related disorders caused by a mutation in one of the using MSC-derived exosomes have multiple
lysosomal exoglycosidases required for the sequen- advantages over MSC-based therapy. The risks
tial degradation of glycosaminoglycans (GAGs), of allogeneic immunological rejection, unwanted
resulting with lysosomal storage in several organs, differentiation, and obstruction of small vessels
includingeyes. MPSVII, alsoknown as Slysyn- by intravenously injected MSCs might be
drome, manifested by corneal clouding, hepatomeg- avoided by therapeutic application of
aly, skeletal dysplasia, short stature, and delayed MSC-derived exosomes that have similar effects
development is caused by a mutation of and migration potential as MSCs. Additionally,
β-glucuronidase which leads to the accumulation exosomes, due to their nano-dimension, can eas-
of heparin sulfate, dermatan sulfate and chondroi- ily pass through biological barriers and enter all
tin-4- and -6-sulfate. Current treatment for MPS VII target organs (Yu et al. 2016).
is transplantation of bone marrow-derived stem Nevertheless, there are still some challenges
cells or enzyme substitution therapy, but neither of that need to be addressed in order to develop
these two therapeutic approaches are effective for MSC-derived exosomes as an effective therapeu-
ameliorating the corneal clouding due to corneal tic agent in the treatment of eye diseases. Further
avascularity. Therefore, corneal clouding is ulti- studies are needed to optimize the injection fre-
mately treated by corneal transplantation (kerato- quency and dose to maintain the long-lasting
plasty) which requires general anesthetic which is effects of MSC-derived exosomes. Moreover,
usually not possible in MPS VII patients suffering having in mind that exosomes are highly hetero-
from respiratory dysfunction and/or severe cardio- geneous depending on the tissue origin of MSCs
myopathy. Accordingly, new therapeutic from which they were derived, pre-selection of
approaches are urgently needed for these patients. the most effective tissue source of MSCs-derived
Most recently, Coulson-Thomas and colleagues exosomes is of crucial importance for their further
proposed MSC-derived exosomes as potentially successful use in ophthalmology. Finally, precise
new agents for the treatment of MPS VII patients exosome-containing factors responsible for thera-
(Coulson-Thomas et al. 2013). Results obtained in peutic effects of MSC-derived exosomes should
this study suggest that β-glucuronidase-containing be defined for each eye disease. In this way,
exosomes released from umbilical cord derived defined therapeutic factor could be overexpressed
MSCs (UC-MSCs) are able to successfully enter in MSCs-derived exosomes prior to application in
into host corneal keratocytes and ECs of MPS VII patients maximizing their therapeutic potential
mice (Coulson-Thomas et al. 2013). Furthermore, and efficacy.
UC-MSC-derived exosomes managed to fuse with
the lysosomes within recipient cells, enabling deliv- Acknowledgment Study was supported by Swiss
ering of MSC-derived active β-glucuronidase and National Science Foundation project (SCOPES
IZ73Z0_152454/1), Novartis foundation for medical-
consequent catabolism of accumulated GAGs in
biological research (Grant No.16C197), Serbian Ministry
MPS VII mice. These findings strongly support of Science (ON175069, ON175103), and Faculty of Med-
the hypothesis that UC-MSCs-derived exosomes ical Sciences University of Kragujevac (JP02/09).
have great potential for being successful in treating
Conflict of Interest The authors declare that there is no
MPS VII and other human corneal congenital met-
conflict of interests regarding the publication of this paper.
abolic diseases.