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Vickie Hoi Ying Wong, Lynsey-Dawn Allen, Jasenka Guduric-Fuchs, Reinhold J Medina, Camilo Acuna Medina, Steve Elliman, Paul Loftus, Lisa O'Flynn, Alan W Stitt; CD362+ stromal stem cells (SSCs) promote revascularisation of the retina in a paracrine manner. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):1828.
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© ARVO (1962-2015); The Authors (2016-present)
Current therapies for ischaemic retinopathies, such as diabetic retinopathy and retinal vein occlusion, are limited and do not address the primary vascular insufficiency that underpins these conditions. As a novel therapeutic approach, we have assessed vasoreparative potential of a defined population of human bone marrow-derived SSCs (CD362+SSCs) in the ischaemic retina.
C57/Bl6 mice pups (postnatal day 7, P7) were subjected to an experimental model of oxygen-induced retinopathy by exposure to high oxygen (75% oxygen, 5 days). At P13 mice received a 1µl intravitreal injection in one eye containing Qdot nanocrystal labelled CD362+, CD362-, plastic adherent SSCs (PA-SSCs) or CD362+SSC-conditioned media (CM). Cell numbers delivered were low [1x103], medium [1x104] or high [1x105]. The contralateral eye was injected with vehicle (DMEM) as a control. Three days post-injection, retinal flatmounts were processed and stained with isolectin B4/streptavidin-AlexaFluor488, and imaged using confocal microscopy. Retinal vasculature was quantified using ImageJ software (avascular or neovascular area/total area,%). All data are shown as mean±SEM. Two-tailed paired t-test was used for statistical analysis.
CD362+SSCs localised to the murine retina in a perivascular manner. Intravitreal delivery of CD362+SSCs showed a significantly reduced avascular area than control at medium (P=0.031, n=6) and high cell numbers (P=0.046, n=11). No difference was found for low dose (P=0.507, n=5). CD362-SSCs also promoted revascularisation at medium cell dose only (P=0.038, n=9). PA-SSCs did not have a significant effect on avascular areas for all doses (low: P=0.739, n=4; medium: P=0.085, n=8; high: P=0.741, n=12). This increased revascularisation may be a result of some CD362 cells associating with host vasculature. No difference was found in neovascularisation areas (P>0.050) for all groups. When treated with CD362+SSC-CM, both avascular (P=0.006, n=9) and pre-retinal neovascular areas (P=0.019) were significantly reduced.
As a novel, highly defined population of bone marrow-derived cells, CD362+SSCs associate closely with the host vasculature and promote revascularisation of the ischaemic retina via secretion of complex paracrine factors. These findings suggest that human CD362+SSCs may have utility for cell therapy to address retinal ischaemia.
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