Circulating stem cell vary with NYHA stage in heart failure patients

Cinzia Fortini, Barbara Toffoletto, Alessandro Fucili, Elisa Puppato, Adriana Olivares, Antonio Paolo Beltrami, Valeria Fiorelli, Natascha Bergamin, Daniela Cesselli, Cristina Morelli, Gloria Francolini, Roberto Ferrari, Carlo Alberto Beltrami

Research output: Contribution to journalArticle

Abstract

We have investigated the blood levels of sub-classes of stem cells (SCs) [mesenchymal stem cells (MSCs), haematopoietic stem cells (HSCs), endothelial progenitor cells/circulating endothelial cells (EPCs/CECs) and tissue-committed stem cells (TCSCs)] in heart failure (HF) patients at different stage of pathology and correlated it with plasmatic levels of proangiogenic cytokines. Peripheral blood level of SCs were analysed 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, vascular endothelial growth factor (VEGF), SDF-1α, TNF-α and NTproBNP were also measured. Compared with healthy individuals, MSC, and in particular the sub-classes 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 +, 1.4versus13.3 cells/μl in controls and NYHA class III patients, respectively) and TCSC (CD45 -CD34 +CXCR4 +, 1.5 cells/μl in controlsversus12.4 and 28.6 cells/μl in NYHA classes II and IV, respectively) were also observed. All tested cytokines were enhanced in HF patients. In particular, for PDGF-BB and SDF-1α we studied specific ligand/receptors pairs. Interestingly, the first one positively correlated with TCSCs expressing PDGFR (r= 0.52,P= 0.001), whereas the second one correlated with TCSCs (r= 0.34,P= 0.005) and with MSCs CD90 + expressing CXCR4 (r= 0.39,P= 0.001). 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.

Original languageEnglish
Pages (from-to)1726-1736
Number of pages11
JournalJournal of Cellular and Molecular Medicine
Volume15
Issue number8
DOIs
Publication statusPublished - Aug 2011

Keywords

  • Cytokines
  • Endothelial progenitor cells
  • Haematopoietic stem cells
  • Heart failure
  • Mesenchymal stem cells
  • Myocardial repair

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Medicine

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  • Cite this

    Fortini, C., Toffoletto, B., Fucili, A., Puppato, E., Olivares, A., Beltrami, A. P., Fiorelli, V., Bergamin, N., Cesselli, D., Morelli, C., Francolini, G., Ferrari, R., & Beltrami, C. A. (2011). Circulating stem cell vary with NYHA stage in heart failure patients. Journal of Cellular and Molecular Medicine, 15(8), 1726-1736. https://doi.org/10.1111/j.1582-4934.2010.01195.x