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Sergio Li Calzi, Lynn C Shaw, William Christopher Shelley, Xiaoping Qi, Judith Quigley, Leni Moldovan, Snow Wu, Mircea Ivan, Michael E Boulton, Mervin Yoder, Maria B Grant; Rescue of ECFCs by CD34+ cells via paracrine factors in a Mouse Model of Retinopathy of Prematurity (ROP). Invest. Ophthalmol. Vis. Sci. 201657(12):.
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© 2017 Association for Research in Vision and Ophthalmology.
Available interventions to reduce neovascularization (NV) in ROP consist of cryotherapy, laser and/or anti-VEGF antibody injections . We asked if intravitreal administration of the reparative populations, CD34+ cells (bone marrow-derived) and/or endothelial colony forming cells (ECFCs) (vascular wall-derived) could protect the retina by promoting vascular regrowth and inhibition of NV.
Oxygen-induced retinopathy (OIR) mouse model was used. Each pup received a single intravitreal injection of cells (human CD34+ isolated from peripheral blood, 10,000 cells; ECFCs- cord blood derived and expanded in culture, 100,000 cells; combination CD34++ECFCs, 110,000 cells). Experimental groups differed based on injection/euthanasia times (P5/P12, P5/P17, P12/P17). Whole retinas were stained with collagen IV antibodies and retinal vaso-obliteration and NV were measured in the respective regions. Immunohistochemical localization of injected cells was performed using confocal microscopy. ERG analysis was performed at P17, P24 and P31.
Maximum vaso-obliteration was seen in the saline and CD34+ pups of the P5/P12 group (Saline=22.3±0.4%; CD34+=23.4±0.8%, p=0.1), while ECFCs and CD34+/ECFCs (Combo) showed significant reduction (ECFCs=18.4±1.3%, p<0.05; Combo=20.0±0.7%, p<0.05). Cell injection at P12 reduced vaso-obliteration in all groups when compared to saline (Saline=13.9±0.9%; CD34+=5.7±1.0%, p<0.05; ECFC=8.1±0.7%, p<0.05; Combo=7.4±1.0%, p<0.05) and reduced NV (Saline=13.3±1.3%; CD34+=3.5±1.1%, p<0.05; ECFC=2.8±0.7%, p<0.05; Combo=4.1±0.6%, p<0.05). Injection of either cell type alone at P5 resulted in NV levels similar to saline controls at P17; however, the combination of cells prevented NV. P5-injected ECFCs incorporated into, and stimulated Deep Vascular Plexus formation by P12. ERG analysis demonstrated a loss of neural retinal function by P24 in the OIR model with restoration of function by P31. Injection of cells showed no detrimental effects.
CD34+ cells and ECFCs reduced retinal vaso-obliteration and NV. In a hyperoxic environment, ECFC survival was improved by release of paracrine factors from CD34+ cells. The combination of these two cell types showed advantages to single populations in prevention of NV.
This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.
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