International Journal of Stem Cells

Korean Society for Stem Cell Research (한국줄기세포학회)
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Regenerative Effect of Adipose Derived Mesenchymal Stem Cells on Ganglion Cells in the Hypoxic Organotypic Retina Culture

  • Meital Ben Dov (Department of Ophthalmology, Tel-Aviv Sourasky Medical Center) ;
  • Bryan Krief (Department of Ophthalmology, Tel-Aviv Sourasky Medical Center) ;
  • Moshe Benhamou (Department of Ophthalmology, Tel-Aviv Sourasky Medical Center) ;
  • Ainat Klein (Department of Ophthalmology, Tel-Aviv Sourasky Medical Center) ;
  • Shula Schwartz (Department of Ophthalmology, Tel-Aviv Sourasky Medical Center) ;
  • Anat Loewenstein (Department of Ophthalmology, Tel-Aviv Sourasky Medical Center) ;
  • Adiel Barak (Department of Ophthalmology, Tel-Aviv Sourasky Medical Center) ;
  • Aya Barzelay (Department of Ophthalmology, Tel-Aviv Sourasky Medical Center)
  • Received : 2022.03.15
  • Accepted : 2022.09.21
  • Published : 2023.05.30
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Abstract

Background and Objectives: To examine whether ischemic retinal ganglion cells (RGCs) will be salvaged from cell death by human adipose-derived mesenchymal stem cells (ADSCs) in an organotypic retina model. Methods and Results: Deprived of arterial oxygen supply, whole mice retinas were cultured as an ex vivo organotypic cultures on an insert membrane in a 24-well plate. The therapeutic potential of ADSCs was examined by co-culture with organotypic retinas. ADSCs were seeded on top of the RGCs allowing direct contact, or at the bottom of the well, sharing the same culture media and allowing a paracrine activity. The number of surviving RGCs was assessed using Brn3a staining and confocal microscopy. Cytokine secretion of ADSCs to medium was analyzed by cytokine array. When co-cultured with ADSCs, the number of surviving RGCs was similarly significantly higher in both treatment groups compared to controls. Analysis of ADSCs cytokines secretion profile, showed secretion of anti-apoptotic and pro-proliferative cytokines (threshold>1.4). Transplantation of ADSCs in a co-culture system with organotypic ischemic retinas resulted in RGCs recovery. Since there was no advantage to direct contact of ADSCs with RGCs, the beneficial effect seen may be related to paracrine activity of ADSCs. Conclusions: These data correlated with secretion profile of ADSCs' anti-apoptotic and pro-proliferative cytokines.

Keywords

Acknowledgement

This study was supported from Orion grant (213310).

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