Objectives- Circulating angiogenic cells (CACs) are vascular-committed bone-marrow derived cells expressing endothelial and stem cell markers that are dysfunctional in type 1 diabetes (T1D). We studied if restoration of endogenous beta cells function with islet transplantation is associated with better CACs function. Research design and methods- 18 T1D patients, 14 insulin independent islet-transplanted patients (ITA) and 14 healthy controls (C) were studied cross-sectionally. In vivo (CACs percentage/apoptosis and migratory/differentiation assay) and in vitro studies [colony forming unit endothelial cells (CFU-ECs) counting, CACs percentage/apoptosis, cytokine production and migratory/differentiation assay] were performed, together with endothelial dependent dilatation (EDD) test in vivo. The addition of serial concentrations IL-8 and anti-IL8 in vitro cultures was performed to assess IL-8 mediated cell survival/apoptosis. Results- The percentage of alive and apoptotic CACs did not differ among the 3 groups. CFU-ECs absolute number obtained from T1D, but not from ITA, was reduced compared to C (C=7.3±1.9, T1D=0.9±0.4 and ITA=4.7±1.9; p<0.05 T1D vs. all), in vitro SDF-1α mediated migration/differentiation was similar among patients while in vivo angiogenesis assay showed a better angiogenic ability of ITA compared to T1D (capillary density: C=93.5±22.1, T1D=19.2±2.8 and ITA=44.0±10.5, p<0.05 T1D vs. all). Higher apoptotic rate (C=1.9±0.4, T1D=7.4±2.4 and ITA=2.2±0.9 %; p=0.007 T1D vs. C) and lower IL-8 secretion (C=24778 4324, T1D=5870 1163 and ITA=15480 2125 pg/ml; p=0.01 T1D vs. all) were evident in CFU-ECs obtained from T1D compared to C and ITA. In vitro addition of anti-hIL-8 to CFU-ECs reduced the number of CFU-ECs from C abrogating the beneficial effect of normoglycemia. On the contrary adding rhIL-8 did not rescue the reduced CFU-EC number observed in T1D. Finally, T1D, but not ITA, had a lower EDD compared with C (C=8.6±0.6, T1D=4.1±1.4 and ITA=16.4±2.3 %; p<0.001 T1D vs. all). Conclusions- CACs function is altered in T1D and can be restored after islet transplantation.
Improved function of circulating angiogenic cells is evident in type 1 diabetic islet-transplanted patients
Maffi P;SECCHI , ANTONIO;
2010-01-01
Abstract
Objectives- Circulating angiogenic cells (CACs) are vascular-committed bone-marrow derived cells expressing endothelial and stem cell markers that are dysfunctional in type 1 diabetes (T1D). We studied if restoration of endogenous beta cells function with islet transplantation is associated with better CACs function. Research design and methods- 18 T1D patients, 14 insulin independent islet-transplanted patients (ITA) and 14 healthy controls (C) were studied cross-sectionally. In vivo (CACs percentage/apoptosis and migratory/differentiation assay) and in vitro studies [colony forming unit endothelial cells (CFU-ECs) counting, CACs percentage/apoptosis, cytokine production and migratory/differentiation assay] were performed, together with endothelial dependent dilatation (EDD) test in vivo. The addition of serial concentrations IL-8 and anti-IL8 in vitro cultures was performed to assess IL-8 mediated cell survival/apoptosis. Results- The percentage of alive and apoptotic CACs did not differ among the 3 groups. CFU-ECs absolute number obtained from T1D, but not from ITA, was reduced compared to C (C=7.3±1.9, T1D=0.9±0.4 and ITA=4.7±1.9; p<0.05 T1D vs. all), in vitro SDF-1α mediated migration/differentiation was similar among patients while in vivo angiogenesis assay showed a better angiogenic ability of ITA compared to T1D (capillary density: C=93.5±22.1, T1D=19.2±2.8 and ITA=44.0±10.5, p<0.05 T1D vs. all). Higher apoptotic rate (C=1.9±0.4, T1D=7.4±2.4 and ITA=2.2±0.9 %; p=0.007 T1D vs. C) and lower IL-8 secretion (C=24778 4324, T1D=5870 1163 and ITA=15480 2125 pg/ml; p=0.01 T1D vs. all) were evident in CFU-ECs obtained from T1D compared to C and ITA. In vitro addition of anti-hIL-8 to CFU-ECs reduced the number of CFU-ECs from C abrogating the beneficial effect of normoglycemia. On the contrary adding rhIL-8 did not rescue the reduced CFU-EC number observed in T1D. Finally, T1D, but not ITA, had a lower EDD compared with C (C=8.6±0.6, T1D=4.1±1.4 and ITA=16.4±2.3 %; p<0.001 T1D vs. all). Conclusions- CACs function is altered in T1D and can be restored after islet transplantation.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
