Intravitreal injection of Clonal Bone Marrow-Derived Mesenchymal Stem Cells-Derived Extracellular vesicles promotes retinal ganglion cell survival after optic nerve crush injury in rats

Elahe sadat Mirsane1 , Sara Poosty2 , Faezeh Shekari3 , Hamid Sadeghi-abandansari4 , Mohammad-Hossein Ghanian5 , Hossein Baharvand6 , Leila Satarian7 *

  1. Department of Brain and Cognitive Sciences, Cell Science Research Center, Royan Institute for Stem Cell. Biology and Technology, ACECR, Tehran, Iran
  2. Department of Brain and Cognitive Sciences, Cell Science Research Center, Royan Institute for Stem Cell. Biology and Technology, ACECR, Tehran, Iran
  3. Department of Stem cell and development Biology, Cell Science Research Center, Royan Institute for Stem Cell. Biology and Technology, ACECR, Tehran, Iran
  4. Department of Cell Engineering, Cell Science Research Center, Royan Institute for Stem Cell. Biology and Technology, ACECR, Tehran, Iran.Department of cancer Medicine, Cell Science Research Center, Royan Institute for Stem Cell. Biology and Technology, ACECR,Isar,Babol,Iran.
  5. Department of Cell Engineering, Cell Science Research Center, Royan Institute for Stem Cell. Biology and Technology, ACECR, Tehran, Iran.
  6. Department of Brain and Cognitive Sciences, Cell Science Research Center, Royan Institute for Stem Cell. Biology and Technology, ACECR, Tehran, Iran.Department of Development Biology, University of Science and culture, Tehran, Iran.
  7. Department of Brain and Cognitive Sciences, Cell Science Research Center, Royan Institute for Stem Cell. Biology and Technology, ACECR, Tehran, Iran.

Abstract: The number of optic nerve damage cases as a result of the indirect effects of diseases or direct blows to the head yet are incurable. Existing drug and surgical treatment only reduce the progress of this disorder. In recent years, handle these injuries by using mesenchymal stem cells (MSCs) in both preclinical and clinical trials have been shown improving vision outcome. Although MSCs have shown acceptable results in recent studies but its clonal-type are superior due to their advantages such as homogeneity and greater passagebility. As recent studies in the animal model of optic nerve crush show that the use of extracellular vehicles (EVs) have better effect in compare with cell therapy, in this study, we investigated the therapeutic effect of ClonalMSCs derived extracellular vesicles.

Methods: Characterized human clonal-MSCs derived extracellular vesicles prepared from EVs Royan Institute Bank. 10 µg from the EVs/PBS were applied to an optic nerve crushed rat model as intravitreally. Then optokinetic response assessed as visual behavioral test on 7th and 60th days post injury. Then survival retinal cells rate was evaluated by Whole retinal staining.

Results: We found that rat visual behavioral have better-quality in EVs group compared to PBS in both acute and chronic phase post injury. Also, this result confirmed in EV-receiving group by more significant survived retinal ganglion cells which stained with Brn3a.

Conclusion: This study supports the use of human clonal-MSCs derived extracellular vesicles as a cell-free therapy to Protect injured ganglion cells during optic nerve disease. Further studies are needed to determine the probable side effects of this EVs applying.





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