July 2019
Volume 60, Issue 9
Free
ARVO Annual Meeting Abstract  |   July 2019
Pre-treatment of Endothelial Colony Forming Cells (ECFCs) with a novel anti-oxidant enhances their vasoregenerative potential.
Author Affiliations & Notes
  • Stuart McKeown
    Queen's University Belfast, Belfast, NORTHERN IRELAND, United Kingdom
  • Paul Canning
    Queen's University Belfast, Belfast, NORTHERN IRELAND, United Kingdom
  • Caroline Barelle
    Elasmogen, United Kingdom
  • Fiona Cunningham
    Queen's University Belfast, Belfast, NORTHERN IRELAND, United Kingdom
  • Donald McPhail
    Antoxis Ltd, United Kingdom
  • Andrew J.R Porter
    School of Medical Sciences, University of Aberdeen, United Kingdom
    Elasmogen, United Kingdom
  • Reinhold J. Medina
    Queen's University Belfast, Belfast, NORTHERN IRELAND, United Kingdom
  • Alan W Stitt
    Queen's University Belfast, Belfast, NORTHERN IRELAND, United Kingdom
  • Footnotes
    Commercial Relationships   Stuart McKeown, None; Paul Canning, None; Caroline Barelle, Elasmogen (S); Fiona Cunningham, None; Donald McPhail, Antoxis Ltd, (E); Andrew Porter, Antoxis Ltd, (S), Elasmogen (S); Reinhold Medina, None; Alan Stitt, None
  • Footnotes
    Support  None
Investigative Ophthalmology & Visual Science July 2019, Vol.60, 1663. doi:
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      Stuart McKeown, Paul Canning, Caroline Barelle, Fiona Cunningham, Donald McPhail, Andrew J.R Porter, Reinhold J. Medina, Alan W Stitt; Pre-treatment of Endothelial Colony Forming Cells (ECFCs) with a novel anti-oxidant enhances their vasoregenerative potential.. Invest. Ophthalmol. Vis. Sci. 2019;60(9):1663.

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

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Abstract

Purpose : ECFCs have considerable potential as therapeutic cells to achieve vascular regeneration in the ischaemic retina and choroid. Whilst ECFCs have proven reparative efficacy, we sought to determine if their function could be enhanced prior to delivery into the pro-inflammatory and pro-oxidative microenvironment which characterises ischaemic tissues. This study has evaluated the potential for a novel synthetic flavonoid, ELN/41 or Proxison™ (7-decyl-3-hydroxy-2-(3,4,5-trihydroxyphenyl)-4-chromenone) to enhance ECFC function.

Methods : ECFCs isolated from umbilical cord blood, were pre-treated with 5 µM ELN/41. ELN/41 auto-fluoresces green and the localisation of the agent was assessed via confocal microscopy . ECFCs were exposed to 10 µM hydrogen peroxide (H2O2) to simulate a pro-oxidative environment while other cells were treated with ELN/41 or the vehicle (veh) alone. Clonogenic ECFC assays were assessed over 5-6 days and colonies enumerated. ECFC barrier formation was assessed via Xcelligence. Stable ECFC monolayers were treated with thrombin and permeability response quantified. Integration of control and ELN/41 treated ECFCs into choroidal explants from P8 C57BL/6J mice were assessed for angiogenic response over 5 days. Results were analysed by one way ANOVA.

Results : ELN/41 localised to ECFC mitochondria. The clonogenic capacity of ECFCs treated with ELN/41 was significantly increased compared to those without treatment (p=<0.001). ELN/41 treatment improved migration of ECFCs in H2O2, whilst non-treated ECFCs showed decreased wound closure after 6hrs versus pre-treated cells (p=<0.001) and veh control (p=<0.001). H2O2 exposed ECFCs had impaired barrier properties compared to those pre-treated with ELN/41 (p=<0.01) and veh controls (p=<0.001). ECFCs integrated with, and significantly enhanced the angiogenic sprouting of choroidal explants compared to those without ECFCs (p=<0.001). Explants treated with H2O2 had decreased angiogenesis versus control explants (p=<0.01) and explants in co-culture with ELN/41 treated cells.

Conclusions : While ECFCs possess endogenous anti-oxidant capacity, these cells show diminished function when exposed to a pro-oxidant insult. Priming ECFCs with ELN/41 imparts a potent protective effect and suggests potential for enhancing the reparative function in the context of cell therapy into ischaemic retina and choroid.

This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.

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