Disturbed angiogenic activity of adipose-derived stromal cells obtained from patients with coronary artery disease and diabetes mellitus type 2

• Published in: Journal of translational medicine 2014-12, Vol.12 (1), p.337-337, Article 337
• Main Authors: Dzhoyashvili, Nina A, Efimenko, Anastasia Yu, Kochegura, Tatiana N, Kalinina, Natalia I, Koptelova, Natalia V, Sukhareva, Olga Yu, Shestakova, Marina V, Akchurin, Renat S, Tkachuk, Vsevolod A, Parfyonova, Yelena V
• Format: Article
• Language: English
• Subjects: Adipose Tissue - pathology; Adipose tissues; Adult; Aged; Analysis; Care and treatment; Chronic diseases; Coronary Artery Disease - complications; Coronary Artery Disease - pathology; Coronary heart disease; Coronary vessels; Development and progression; Diabetes; Diabetes Mellitus, Type 2 - complications; Diabetes Mellitus, Type 2 - pathology; Drug therapy; Female; Health aspects; Heart attacks; Humans; Male; Medical research; Metabolic disorders; Middle Aged; Neovascularization, Pathologic; Stromal Cells - pathology; Studies; Telomeres; Vascular endothelial growth factor
• ISSN: 1479-5876; 1479-5876
• DOI: 10.1186/s12967-014-0337-4

Multipotent mesenchymal stem/stromal cells (MSC) including adipose-derived stromal cells (ADSC) have been successfully applied for cardiovascular diseases treatment. Their regenerative potential is considered due to the multipotency, paracrine activity and immunologic privilege. However, therapeutic efficacy of autologous MSC for myocardial ischemia therapy is modest. We analyzed if ADSC properties are attenuated in patients with chronic diseases such as coronary artery disease (CAD) and diabetes mellitus type 2 (T2DM). ADSC were isolated from subcutaneous fat tissue of patients without established cardiovascular diseases and metabolic disorders (control group, n = 19), patients with CAD only (n = 32) and patients with CAD and T2DM (n = 28). ADSC phenotype (flow cytometry) was CD90(+)/CD73(+)/CD105(+)/CD45(-)/CD31(-) and they were capable of adipogenic and osteogenic differentiation. ADSC morphology and immunophenotype were similar for all patients, but ADSC from patients with CAD and T2DM had higher proliferation activity and shorter telomeres compared to control patients. ADSC conditioned media stimulated capillary-like tubes formation by endothelial cells (EA.hy926), but this effect significantly decreased for patients with CAD (p = 0.03) and with CAD + T2DM (p = 0.017) compared to the control group. Surprisingly we revealed significantly higher secretion of some pro-angiogenic factors (ELISA) by ADSC: vascular endothelial growth factor (VEGF) and hepatocyte growth factor (HGF) for patients with CAD and HGF and placental growth factor (PlGF) for patients with CAD + T2DM. Among angiogenesis inhibitors such as thrombospondin-1, endostatin and plasminogen activator inhibitor-1 (PAI-1) level of PAI-1 in ADSC conditioned media was significantly higher for patients with CAD and CAD + T2DM compared to the control group (p