Impaired function of circulating CD34(+) CD45(-) cells in patients with proliferative diabetic retinopathy.
Proliferative diabetic retinopathy is a consequence of retinal ischemia due to capillary occlusion resulting from damage to the retinal microvascular endothelium. Recent evidence suggests that high levels of bone-marrow derived circulating endothelial progenitor cells (EPCs) contribute to the pathological neovascularization of ischemic tissues and are a critical risk factor for the development of these complications. In the absence of a consensus definition of a circulating EPC and its surface markers in humans we evaluated the functional properties of CD34(+) CD45(-) endothelial colony forming cells (ECFCs) in patients with proliferative diabetic retinopathy (PDR). Higher levels of circulating CD34(+) CD45(-) cells were observed in patients with PDR compared to controls. However, ECFCs from patients with PDR were impaired in their ability to migrate towards SDF-1 and human serum, incorporate into and form vascular tubes with human retinal endothelial cells. The results from these pilot studies suggest that ECFCs from patients with PDR are mobilized into the circulation but may be unable to migrate and repair damaged capillary endothelium. This suggests that ECFCs may be a potential therapeutic target in the prevention and treatment of diabetic vascular complications.
Tan
Kevin
K
Department of Ophthalmology, Cleveland Clinic Lerner College of Medicine, Cleveland Clinic, Cleveland, OH 44195, USA.
Lessieur
Emma
E
Cutler
Alecia
A
Nerone
Patrice
P
Vasanji
Amit
A
Asosingh
Kewal
K
Erzurum
Serpil
S
Anand-Apte
Bela
B
D018952:Antigens, CD34 / Q000378:metabolism*; D015153:Blotting, Western; D002465:Cell Movement; D002478:Cells, Cultured; D054377:Chemokine CXCL12 / Q000097:blood; D003930:Diabetic Retinopathy / Q000097:blood / Q000503:physiopathology*; D004730:Endothelium, Vascular / Q000378:metabolism / Q000503:physiopathology*; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D016130:Immunophenotyping; D017493:Leukocyte Common Antigens / Q000378:metabolism*; D007963:Leukocytes, Mononuclear / Q000502:physiology; D020411:Oligonucleotide Array Sequence Analysis; D015861:Retinal Neovascularization / Q000097:blood / Q000503:physiopathology*; D012171:Retinal Vessels / Q000378:metabolism / Q000503:physiopathology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013234:Stem Cells / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000097:blood; D014822:Vitreous Body / Q000378:metabolism
D018952:Antigens, CD34; D054377:Chemokine CXCL12; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D017493:Leukocyte Common Antigens; C516769:PTPRC protein, human