Aim. We have investigated the blood levels of subclasses of stem cells (SCs) [mesenchymal stem cells (MSCs), hematopoietic stem cells (HSCs), endothelial progenitor cells/circulating endothelial cells (EPCs/CECs) and tissue-committed stem cells (TCSCs)] in HF patients at different stage of pathology and correlated it with plasmatic levels of proangiogenic cytokines. Results. Peripheral blood level of SCs were analyzed in 97 HF patients (24 in NYHA class I, 41 in class II, 17 in class III and 15 in class IV) and in 23 healthy controls. Plasmatic levels of PDGF-BB, bFGF, HGF, VEGF, SDF-1α, TNF-α and NTproBNP were also measured. Compared with healthy subjects, MSC, and in particular the subclasses CD45−CD34−CD90+, CD45−CD34−CD105+ and CD45−CD34−CXCR4+were significantly enhanced in NYHA class IV patients (16.8, 6.4 and 2.7 fold respectively). Level of CD45−CD34−CD90+CXCR4+cells progressively increased from class II to class IV (fold increases compared with controls: 8.5, 12 and 21.5 respectively). A significant involvement of CXCR4+ subpopulation of HSC (CD45+CD34+CD90+CXCR4+, 1.4 vs. 13.3 cells/μl in controls and NYHA class III patients respectively) and TCSC (CD45−CD34+CXCR4+, 1.5 cells/μl in controls vs. 12.4 and 28.6 cells/μl in NYHA class II and IV respectively) were also observed. All tested cytokines were enhanced in HF patients. In particular, for PDGF-BB and SDF-1 alpha we studied specific ligand/receptors pairs. Interestingly, the first one positively correlated with TCSCs expressing PDGFR (r=0.52, p=0.001), while the second one correlated with TCSCs (r=0.34, p=0.005) and with MSCs CD90+expressing CXCR4 (r=0.39, p=0.001). Conclusions. HF is characterized by the increase in the circulating levels of different MSC, HSC, EPC and TCSC subsets. Both the entity and kinetic of this process varied in distinct cell subsets. Specifically, differently from HSCs and EPCs/CECs, MSCs and TCSCs significantly increased with the progression of the disease, suggesting a possible distinct role of these cells in the pathophysiology of HF.

Circulating stem cells vary with NYHA stage in heart failure patients

FORTINI, Cinzia;A. Fucili;FERRARI, Roberto
Penultimo
;
2011

Abstract

Aim. We have investigated the blood levels of subclasses of stem cells (SCs) [mesenchymal stem cells (MSCs), hematopoietic stem cells (HSCs), endothelial progenitor cells/circulating endothelial cells (EPCs/CECs) and tissue-committed stem cells (TCSCs)] in HF patients at different stage of pathology and correlated it with plasmatic levels of proangiogenic cytokines. Results. Peripheral blood level of SCs were analyzed in 97 HF patients (24 in NYHA class I, 41 in class II, 17 in class III and 15 in class IV) and in 23 healthy controls. Plasmatic levels of PDGF-BB, bFGF, HGF, VEGF, SDF-1α, TNF-α and NTproBNP were also measured. Compared with healthy subjects, MSC, and in particular the subclasses CD45−CD34−CD90+, CD45−CD34−CD105+ and CD45−CD34−CXCR4+were significantly enhanced in NYHA class IV patients (16.8, 6.4 and 2.7 fold respectively). Level of CD45−CD34−CD90+CXCR4+cells progressively increased from class II to class IV (fold increases compared with controls: 8.5, 12 and 21.5 respectively). A significant involvement of CXCR4+ subpopulation of HSC (CD45+CD34+CD90+CXCR4+, 1.4 vs. 13.3 cells/μl in controls and NYHA class III patients respectively) and TCSC (CD45−CD34+CXCR4+, 1.5 cells/μl in controls vs. 12.4 and 28.6 cells/μl in NYHA class II and IV respectively) were also observed. All tested cytokines were enhanced in HF patients. In particular, for PDGF-BB and SDF-1 alpha we studied specific ligand/receptors pairs. Interestingly, the first one positively correlated with TCSCs expressing PDGFR (r=0.52, p=0.001), while the second one correlated with TCSCs (r=0.34, p=0.005) and with MSCs CD90+expressing CXCR4 (r=0.39, p=0.001). Conclusions. HF is characterized by the increase in the circulating levels of different MSC, HSC, EPC and TCSC subsets. Both the entity and kinetic of this process varied in distinct cell subsets. Specifically, differently from HSCs and EPCs/CECs, MSCs and TCSCs significantly increased with the progression of the disease, suggesting a possible distinct role of these cells in the pathophysiology of HF.
2011
Fortini, Cinzia; Toffoletto, B.; Fucili, A.; Puppato, E.; Olivares, A.; Beltrami, A. P.; Fiorelli, V.; Bergamin, N.; Cesselli, D.; Morelli, C.; Francolini, G.; Ferrari, Roberto; Beltrami, C. A.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11392/1405511
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