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The aim of this study was to compare the serum levels of the anti-angiogenic factor endostatin (S-endostatin) as a potential marker of vasculogenesis after autologous cell therapy (ACT) versus percutaneous transluminal angioplasty (PTA) in diabetic patients with critical limb ischemia (CLI). A total of 25 diabetic patients with CLI treated in our foot clinic during the period 2008–2014 with ACT generating potential vasculogenesis were consecutively included in the study; 14 diabetic patients with CLI who underwent PTA during the same period were included in a control group in which no vasculogenesis had occurred. S-endostatin was measured before revascularization and at 1, 3, and 6 months after the procedure. The effect of ACT and PTA on tissue ischemia was confirmed by transcutaneous oxygen pressure (TcPO 2 ) measurement at the same intervals. While S-endostatin levels increased significantly at 1 and 3 months after ACT (both P < 0.001), no significant change of S-endostatin after PTA was observed. Elevation of S-endostatin levels significantly correlated with an increase in TcPO 2 at 1 month after ACT ( r = 0.557; P < 0.001). Our study showed that endostatin might be a potential marker of vasculogenesis because of its significant increase after ACT in diabetic patients with CLI in contrast to those undergoing PTA. This increase may be a sign of a protective feedback mechanism of this anti-angiogenic factor.

The release of proangiogenic cytokines into the circulation after stem cell (SC) therapy and compensatory increase of angiogenesis inhibitors may reflect local vasculogenesis but also can increase the risk of side effects. The aim of our study was to evaluate serum levels of angiogenic cytokines with regard to the assessment of local and systemic vasculogenesis in diabetic patients with no-option critical limb ischemia (NO-CLI). Twenty-five diabetic patients with NO-CLI treated with SCs isolated from bone marrow or stimulated peripheral blood were included in the study. Serum levels of proangiogenic cytokines (VEGF, bFGF, Ang-1, PDGF-AA, and PDGF-BB) and an antiangiogenic cytokine (endostatin) were assessed 6 months after cell treatment, compared to baseline values, and correlated with the number of injected CD34 + cells. The clinical effect of SC therapy (assessed by changes in TcPO 2 ) and potential systemic vasculogenesis (assessed by eye fundus examination) were evaluated after 6 months. Serum levels of angiogenic inhibitor endostatin increased significantly after 1 and 3 months ( p = 0.0003), but no significant increase in serum levels of proangiogenic cytokines was observed. A significant correlation between number of injected CD34 + cells and serum levels of endostatin was observed ( r = 0.41, p < 0.05); however, proangiogenic cytokines did not correlate with CD34 + cells. No correlation between increase in TcPO 2 after treatment and serum levels of any of the angiogenic cytokines were seen, and no signs of systemic vasculogenesis in the retina were observed after 6 months. Despite the significant increase in the levels of the angiogenic inhibitor endostatin following SC treatment, there was no risk of systemic vasculogenesis after SC therapy as documented by serum levels of proangiogenic cytokines or changes in the retina.