Preclinical evaluation and optimization of a cell therapy using human cord blood-derived endothelial colony-forming cells for ischemic retinopathies

Reid, E. , Guduric-Fuchs, J., O'Neill, C. L., Allen, L.-D., Chambers, S. E.J., Stitt, A. W. and Medina, R. J. (2018) Preclinical evaluation and optimization of a cell therapy using human cord blood-derived endothelial colony-forming cells for ischemic retinopathies. Stem Cells Translational Medicine, 7(1), pp. 59-67. (doi: 10.1002/sctm.17-0187) (PMID:29164803) (PMCID:PMC5746158)

Abstract

Cell therapy using endothelial progenitors holds promise for vascular repair in ischemic retinopathies. Using a well‐defined subpopulation of human cord blood‐derived endothelial progenitors known as endothelial colony‐forming cells (ECFCs), we have evaluated essential requirements for further development of this cell therapy targeting the ischemic retina, including dose response, delivery route, and toxicity. First, to evaluate therapeutic efficacy relating to cell dose, ECFCs were injected into the vitreous of mice with oxygen‐induced retinopathy. Using angiography and histology, we found that intravitreal delivery of low dose (1 × 103) ECFCs was as effective as higher cell doses (1 × 104, 1 × 105) in promoting vascular repair. Second, injection into the common carotid artery was tested as an alternative, systemic delivery route. Intracarotid ECFC delivery conferred therapeutic benefit which was comparable to intravitreal delivery using the same ECFC dose (1 × 105), although there were fewer human cells observed in the retinal vasculature following systemic delivery. Third, cell immunogenicity was evaluated by injecting ECFCs into the vitreous of healthy adult mice. Assessment of murine ocular tissues identified injected cells in the vitreous, while demonstrating integrity of the host retina. In addition, ECFCs did not invade into the retina, but remained in the vitreous, where they eventually underwent cell death within 3 days of delivery without evoking an inflammatory response. Human specific Alu sequences were not found in healthy mouse retinas after 3 days of ECFC delivery. These findings provide supportive preclinical evidence for the development of ECFCs as an efficacious cell product for ischemic retinopathies

• Item Type: Articles
• Additional Information: This research was supported by a grant from the Sir Jules Thorn Trust, the JDRF, the Leverhulme Trust, Fight for Sight, and the National Eye Research Centre.
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Reid, Dr Emma
• Authors: Reid, E., Guduric-Fuchs, J., O'Neill, C. L., Allen, L.-D., Chambers, S. E.J., Stitt, A. W., and Medina, R. J.
• College/School: College of Medical Veterinary and Life Sciences > School of Life Sciences; College of Medical Veterinary and Life Sciences > School of Psychology & Neuroscience
• Journal Name: Stem Cells Translational Medicine
• Publisher: Wiley
• ISSN: 2157-6564
• ISSN (Online): 2157-6580
• Published Online: 28 December 2017
• Copyright Holders: Copyright © 2017 The Authors
• First Published: First published in Stem Cells Translational Medicine 7(1):59-67
• Publisher Policy: Reproduced under a Creative Commons License