**6.2. Therapeutic approaches to replace the injured endothelial cells**

Endothelial cells exposed to oxidative stress and the proinflammatory environment undergo accelerated aging in hyperglycemia, thus stimulation of cell replacement with fresh endothelial cells may help restore the vascular function [126]. While it is difficult to estimate the exact number of endothelial cells, a reduction of progenitor cell count and functionality was detected in diabetes, and it is expected to result in a decreased number of functional endothelial cells in the vasculature [24, 127]. Even in the retina, where neovascularization (proliferative diabetic retinopathy) is the characteristic event, progenitor cell therapy is expected to cause improvement and treat the ischemic vascular abnormalities [165]. Currently, it is difficult to predict which treatment strategy will prove effective in diabetes, but probably the drug-induced enhancement of progenitor cell potency has the highest translational potential in diabetes [166, 167]. Drugs that were suggested for progenitor cell enhancement include statins, losartan (angiotensin II receptor antagonist), aliskiren (direct renin inhibitor), hydrogen sulfide, thymosin β4 and the CXCR4 (C-X-C chemokine receptor type 4) antagonist plerixafor (AMD3100, 1,1-[1,4-Phenylenebis(methylene)]bis-1,4,8,11-tetraazacyclotetradecane) [167]. As some of these drugs are in use in diabetic patients, an evaluation of the effect of these compounds on diabetic progenitor cells might be available in the near future [168]. If mobilization and enhancement of endothelial progenitor cells are achieved, it could help the endothelial recovery in the vasculature in diabetic patients, which may lead to an extension of indication of these drugs.

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