Mesenchymal Stem Cells from Patients With Chronic Heart Failure Display Up-Regulation of Genes Coding for Proinflammatory and Proangiogenic Mediators

Abstract

The purpose of the present study was to evaluate the properties of mesenchymal stem cells (MSC) derived from bone marrow (BM) of patients suffering chronic heart failure (HF). We hypothesized that MSC from patients with HF may display differences in transcription of genes involved in neovascularization and inflammation compared to healthy donors (D). All subjects enrolled (11 healthy donors and 38 HF patients) have given the informed consent. Experiments were held with BM-MSC at passages 3-4 that underwent 15-16 in vitro population doublings. Gene expression was quantified by qPCR. We observed a trend of up-regulation of genes coding for certain proinflammatory cytokines (IL-1α, IL-6, IL-8, MIP-1α) and proangiogenic mediators (angiopoietin-2 (Ang2), HGF, CTGF) in MSC of patients with HF, though the difference was not always significant. The levels of TGFβ1 and VEGF-A gene transcripts did not differ in MSC derived from HF patients and healthy donors.Tabled 1TargetFold changeP vaueTGFβ11.450.44VEGF-A1.270.22Ang23.470.10HGF2.950.15CTGF1.820.01IL-1α2.200.05IL-61.960.05IL-82.060.25MIP-1α2.310.17 Open table in a new tab The observed gene expression changes may be related to the enhanced cellular aging of MSC from HF patients and/or reflect the specific functional alterations of MSC associated with HF. The exact mechanisms of dysregulated transcription of these genes are under our current investigation.