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Therapeutic Potential of Mesenchymal Stem Cell-Derived Exosomes in the Treatment of Eye Diseases

  • C. Randall Harrell
  • Bojana Simovic Markovic
  • Crissy Fellabaum
  • Aleksandar Arsenijevic
  • Valentin Djonov
  • Nebojsa Arsenijevic
  • Vladislav Volarevic
Chapter
Part of the Advances in Experimental Medicine and Biology book series

Abstract

Mesenchymal stem cells (MSCs) were, due to their immunomodulatory and pro-angiogenic characteristics, extensively explored as new therapeutic agents in cell-based therapy of uveitis, glaucoma, retinal and ocular surface diseases.

Since it was recently revealed that exosomes play an important role in biological functions of MSCs, herewith we summarized current knowledge about the morphology, structure, phenotype and functional characteristics of MSC-derived exosomes emphasizing their therapeutic potential in the treatment of eye diseases.

MSC-derived exosomes were as efficient as transplanted MSCs in limiting the extent of eye injury and inflammation. Immediately after intravitreal injection, MSC-derived exosomes, due to nano-dimension, diffused rapidly throughout the retina and significantly attenuated retinal damage and inflammation. MSC-derived exosomes successfully delivered trophic and immunomodulatory factors to the inner retina and efficiently promoted survival and neuritogenesis of injured retinal ganglion cells. MSC-derived exosomes efficiently suppressed migration of inflammatory cells, attenuated detrimental Th1 and Th17 cell-driven immune response and ameliorated experimental autoimmune uveitis. MSC-derived exosomes were able to fuse with the lysosomes within corneal cells, enabling delivering of MSC-derived active β-glucuronidase and consequent catabolism of accumulated glycosaminoglycans, indicating their therapeutic potential in the treatment of Mucopolysaccharidosis VII (Sly Syndrome). Importantly, beneficent effects were noticed only in animals that received MSC-derived exosomes and were not seen after therapy with fibroblasts-derived exosomes confirming specific therapeutic potential of MSCs and their products in the treatment of eye diseases.

In conclusion, MSC-derived exosomes represent potentially new therapeutic agents in the therapy of degenerative and inflammatory ocular diseases.

Keywords

Mesenchymal stem cells Exosomes Eye Injury Inflammation 

Notes

Acknowledgment

Study was supported by Swiss National Science Foundation project (SCOPES IZ73Z0_152454/1), Novartis foundation for medical-biological research (Grant No.16C197), Serbian Ministry of Science (ON175069, ON175103), and Faculty of Medical Sciences University of Kragujevac (JP02/09).

Conflict of Interest The authors declare that there is no conflict of interests regarding the publication of this paper.

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Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  • C. Randall Harrell
    • 1
  • Bojana Simovic Markovic
    • 2
  • Crissy Fellabaum
    • 1
  • Aleksandar Arsenijevic
    • 2
  • Valentin Djonov
    • 3
  • Nebojsa Arsenijevic
    • 2
  • Vladislav Volarevic
    • 2
  1. 1.Regenerative Processing Plant-RPP, LLCPalm HarborUSA
  2. 2.Faculty of Medical Sciences, Center for Molecular Medicine and Stem Cell ResearchUniversity of KragujevacKragujevacSerbia
  3. 3.Institute of AnatomyUniversity of BernBernSwitzerland

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