Investigative Ophthalmology & Visual Science Cover Image for Volume 65, Issue 7
June 2024
Volume 65, Issue 7
Open Access
ARVO Annual Meeting Abstract  |   June 2024
Small Extracellular Vesicles Derived From Pre-Activated Mesenchymal Stromal Cells For Treatment Of Ocular Inflammation And Injury.
Author Affiliations & Notes
  • Thomas Ritter
    Regenerative Medicine Institute, School of Medicine, University of Galway, Galway, Ireland
    CÚRAM, SFI Research Centre for Medical Devices, University of Galway, Galway, Ireland
  • Jiemin Wang
    Regenerative Medicine Institute, School of Medicine, University of Galway, Galway, Ireland
    CÚRAM, SFI Research Centre for Medical Devices, University of Galway, Galway, Ireland
  • Ellen Donohoe
    Regenerative Medicine Institute, School of Medicine, University of Galway, Galway, Ireland
    CÚRAM, SFI Research Centre for Medical Devices, University of Galway, Galway, Ireland
  • Manon Jammes
    Regenerative Medicine Institute, School of Medicine, University of Galway, Galway, Ireland
    CÚRAM, SFI Research Centre for Medical Devices, University of Galway, Galway, Ireland
  • Trung Bach
    Regenerative Medicine Institute, School of Medicine, University of Galway, Galway, Ireland
    CÚRAM, SFI Research Centre for Medical Devices, University of Galway, Galway, Ireland
  • Aoife Canning
    Regenerative Medicine Institute, School of Medicine, University of Galway, Galway, Ireland
    CÚRAM, SFI Research Centre for Medical Devices, University of Galway, Galway, Ireland
  • Aideen Ryan
    CÚRAM, SFI Research Centre for Medical Devices, University of Galway, Galway, Ireland
    Discipline of Pharmacology and Therapeutics, School of Medicine, University of Galway, Galway, Ireland
  • Seyedmohammad Moosavizadeh
    Regenerative Medicine Institute, School of Medicine, University of Galway, Galway, Ireland
    CÚRAM, SFI Research Centre for Medical Devices, University of Galway, Galway, Ireland
  • Footnotes
    Commercial Relationships   Thomas Ritter None; Jiemin Wang None; Ellen Donohoe None; Manon Jammes None; Trung Bach None; Aoife Canning None; Aideen Ryan None; Seyedmohammad Moosavizadeh None
  • Footnotes
    Support  This project received funding from the European Union’s Horizon Europe research and innovation programme under grant agreement no. 101080611. Jiemin Wang acknowledges the financial support from the Chinese Scholarship Council (202006370067). This work was also supported by Science Foundation Ireland 18/EPSRC-CDT/3583 and the Engineering and Physical Sciences Research Council EP/S02347X/1. This work has emanated from research supported in part by a grant from Science Foundation Ireland (SFI) and the European Regional Development Fund (ERDF) under grant number 13/RC/2073_P2. This project has also received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement no. 814439 and received funding by a Government of Ireland Postgraduate Scholarship (GOIPG/2018/1887) supported by funding from the College of Medicine, Nursing and Health Sciences, University of Galway.
Investigative Ophthalmology & Visual Science June 2024, Vol.65, 55. doi:
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      Thomas Ritter, Jiemin Wang, Ellen Donohoe, Manon Jammes, Trung Bach, Aoife Canning, Aideen Ryan, Seyedmohammad Moosavizadeh; Small Extracellular Vesicles Derived From Pre-Activated Mesenchymal Stromal Cells For Treatment Of Ocular Inflammation And Injury.. Invest. Ophthalmol. Vis. Sci. 2024;65(7):55.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : Mesenchymal stromal cells (MSCs) are shown to have pro-repair and immunomodulatory effects. MSCs secrete particles including small extracellular vesicles (MSC-sEV), to mediate their therapeutic effects. Pre-activating or licensing of MSCs by cytokine cocktails can boost their immunomodulatory and tissue repair activities.
The aim of this study was to characterize naïve- and licensed-MSC-sEV and compare their characteristics and pro-repair efficacy in 2D in-vitro models.

Methods : Human bone marrow MSCs were isolated, cultured in xeno-free media, and characterized for surface marker expression with flow cytometry and for differentiation potential. MSCs were exposed to pre-activating medium containing 50 ng/mL TGF-β and 50 ng/mL IFN-γ for 72 hr.
Following, MSC-sEV were isolated from both naïve- and licensed-MSC conditioned medium using size exclusion chromatography columns. MSC-sEV were further characterized following MISEV guidelines for size distribution, morphology, and surface biomarkers with nanoparticle tracking analysis (NTA), transmission electron microscopy (TEM), and flow cytometry, respectively.
Naïve- and licensed-MSC-sEV were applied to human corneal epithelial cells (HCEpi) and human corneal keratocytes (HCK) in 2D in-vitro scratch models to investigate their effects on human corneal cell migration and wound closure properties.

Results : MSC were shown to express CD90, CD73, and CD44, and negative for CD45, CD11b, and HLA-DR surface markers. Besides, MSC could successfully differentiate into adipocyte and osteoblast lineages.
Isolated naïve- and licensed-MSC-sEV were analysed by NTA and TEM having spherical bilayer morphology with a size range around 80 nm. Both naïve- and licensed-MSC-sEV showed similar surface biomarker profile staining positive for CD9, CD63, and CD81 which were slightly increased on pre-activated MSC-sEV.
In the wound healing assay, while both naïve- and licensed-MSC-sEV had therapeutic effects and promoted cell migration, licensed-MSC-sEV were shown to be more effective in HCEpi and HCK wound closure models in-vitro.

Conclusions : sEV were successfully isolated from human bone marrow derived MSC and showed the desired size and morphology. Pre-activated sEV had enhanced therapeutic effects on HCEpi and HCK wound healing 2D in-vitro models. The therapeutic and immunomodulatory efficacy of these MSC-sEVs will be further investigated.

This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.

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