title: Adipose-derived mesenchymal stromal cells from aged patients with coronary artery disease keep mesenchymal stromal cell properties but exhibit characteristics of aging and have impaired angiogenic potential.
abstract: Tissue regeneration is impaired in aged individuals. Adipose-derived mesenchymal stromal cells (ADSCs), a promising source for cell therapy, were shown to secrete various angiogenic factors and improve vascularization of ischemic tissues. We analyzed how patient age affected the angiogenic properties of ADSCs. ADSCs were isolated from subcutaneous fat tissue of patients with coronary artery disease (CAD; n = 64, 43-77 years old) and without CAD (n = 31, 2-82 years old). ADSC phenotype characterized by flow cytometry was CD90(+)/CD73(+)/CD105(+)/CD45(-)/CD31(-) for all samples, and these cells were capable of adipogenic and osteogenic differentiation. ADSCs from aged patients had shorter telomeres (quantitative reverse transcription polymerase chain reaction) and a tendency to attenuated telomerase activity. ADSC-conditioned media (ADSC-CM) stimulated capillary-like tube formation by endothelial cells (EA.hy926), and this effect significantly decreased with the age of patients both with and without CAD. Angiogenic factors (vascular endothelial growth factor, placental growth factor, hepatocyte growth factor, angiopoetin-1, and angiogenin) in ADSC-CM measured by enzyme-linked immunosorbent assay significantly decreased with patient age, whereas levels of antiangiogenic factors thrombospondin-1 and endostatin did not. Expression of angiogenic factors in ADSCs did not change with patient age (real-time polymerase chain reaction); however, gene expression of factors related to extracellular proteolysis (urokinase and its receptor, plasminogen activator inhibitor-1) and urokinase-type plasminogen activator receptor surface expression increased in ADSCs from aged patients with CAD. ADSCs from aged patients both with and without CAD acquire aging characteristics, and their angiogenic potential declines because of decreasing proangiogenic factor secretion. This could restrict the effectiveness of autologous cell therapy with ADSCs in aged patients.
authors.affiliation: Faculty of Medicine, Lomonosov Moscow State University, Moscow, Russian Federation; Russian Cardiology Research and Production Complex, Moscow, Russian Federation.
authors.forename: Anastasia
authors.initials: A
authors.lastname: Efimenko
authors.forename: Nina
authors.initials: N
authors.lastname: Dzhoyashvili
authors.forename: Natalia
authors.initials: N
authors.lastname: Kalinina
authors.forename: Tatiana
authors.initials: T
authors.lastname: Kochegura
authors.forename: Renat
authors.initials: R
authors.lastname: Akchurin
authors.forename: Vsevolod
authors.initials: V
authors.lastname: Tkachuk
authors.forename: Yelena
authors.initials: Y
authors.lastname: Parfyonova
mesh_terms: D000273:Adipose Tissue / Q000166:cytology*; D000328:Adult; D000368:Aged; D000375:Aging / Q000502:physiology*; D042683:Angiopoietin-1 / Q000378:metabolism; D016922:Cellular Senescence / Q000502:physiology*; D002648:Child; D002675:Child, Preschool; D003324:Coronary Artery Disease / Q000473:pathology*; D017077:Culture Media, Conditioned / Q000494:pharmacology; D005260:Female; D017228:Hepatocyte Growth Factor / Q000378:metabolism; D006801:Humans; D006973:Hypertension / Q000473:pathology; D008297:Male; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D008875:Middle Aged; D018919:Neovascularization, Physiologic / Q000502:physiology*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: C467630:ANGPT1 protein, human; D042683:Angiopoietin-1; D017077:Culture Media, Conditioned; C066855:HGF protein, human; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D017228:Hepatocyte Growth Factor
keywords: Adipose-derived stromal cells; Aging; Cell therapy; Coronary artery disease; Therapeutic angiogenesis; Urokinase receptor