Outgrowth endothelial cells: characterization and their potential for reversing ischemic retinopathy.
OBJECTIVE
Endothelial progenitor cells (EPCs) have potential for promoting vascular repair and revascularization of ischemic retina. However, the highly heterogeneous nature of these cells causes confusion when assessing their biological functions. The purpose of this study was to provide a comprehensive comparison between the two main EPC subtypes, early EPCs (eEPCs) and outgrowth endothelial cells (OECs), and to establish the potential of OECs as a novel cell therapy for ischemic retinopathy.


METHODS
Two types of human blood-derived EPCs were isolated and compared using immunophenotyping and multiple in vitro functional assays to assess interaction with retinal capillary endothelial cells and angiogenic activity. OECs were delivered intravitreally in a mouse model of ischemic retinopathy, and flat mounted retinas were examined using confocal microscopy.


RESULTS
These data indicate that eEPCs are hematopoietic cells with minimal proliferative capacity that lack tube-forming capacity. By contrast, OECs are committed to an endothelial lineage and have significant proliferative and de novo tubulogenic potential. Furthermore, only OECs are able to closely interact with endothelial cells through adherens and tight junctions and to integrate into retinal vascular networks in vitro. The authors subsequently chose OECs to test a novel cell therapy approach for ischemic retinopathy. Using a murine model of retinal ischemia, they demonstrated that OECs directly incorporate into the resident vasculature, significantly decreasing avascular areas, concomitantly increasing normovascular areas, and preventing pathologic preretinal neovascularization.


CONCLUSIONS
As a distinct EPC population, OECs have potential as therapeutic cells to vascularize the ischemic retina.
Medina
Reinhold J
RJ
Centre for Vision and Vascular Science, School of Medicine, Dentistry and Biomedical Science, Queen's University Belfast, Belfast, United Kingdom.
O'Neill
Christina L
CL
Humphreys
Mervyn W
MW
Gardiner
Tom A
TA
Stitt
Alan W
AW
D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D002196:Capillaries / Q000166:cytology; D002469:Cell Separation; D002478:Cells, Cultured; D018920:Coculture Techniques; D004195:Disease Models, Animal; D042783:Endothelial Cells / Q000166:cytology* / Q000502:physiology; D005434:Flow Cytometry; D019084:Fluorescent Antibody Technique, Indirect; D018380:Hematopoietic Stem Cell Transplantation; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000502:physiology; D006801:Humans; D016130:Immunophenotyping; D051379:Mice; D008810:Mice, Inbred C57BL; D018613:Microscopy, Confocal; D015427:Reperfusion Injury / Q000473:pathology / Q000628:therapy*; D012164:Retinal Diseases / Q000473:pathology / Q000628:therapy*; D012171:Retinal Vessels / Q000166:cytology
D015415:Biomarkers