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

• Published in: Stem cells translational medicine 2014-01, Vol.3 (1), p.32-41
• Main Authors: Efimenko, Anastasia, Dzhoyashvili, Nina, Kalinina, Natalia, Kochegura, Tatiana, Akchurin, Renat, Tkachuk, Vsevolod, Parfyonova, Yelena
• Format: Article
• Language: English
• Subjects: Adipose Tissue - cytology; Adipose-derived stromal cells; Administrative support; Adult; Age; Aged; Aging; Aging - physiology; Angina pectoris; Angiogenesis; Angiopoietin-1 - metabolism; Atherosclerosis; Bone marrow; Cardiology; Cardiovascular disease; Cell therapy; Cellular Senescence - physiology; Child; Child, Preschool; Coronary artery; Coronary artery disease; Coronary Artery Disease - pathology; Coronary vessels; Culture Media, Conditioned - pharmacology; Data analysis; Diabetes; Female; Heart diseases; Heart failure; Hepatocyte Growth Factor - metabolism; Humans; Hypertension; Hypertension - pathology; Ischemia; Male; Mesenchymal stem cells; Mesenchymal Stromal Cells - cytology; Mesenchymal Stromal Cells - drug effects; Mesenchymal Stromal Cells - metabolism; Mesenchyme; Middle Aged; Neovascularization, Physiologic - physiology; Pathology; Patients; Secretion; Stromal cells; Studies; Surgery; Therapeutic angiogenesis; Tissue-Specific Progenitor and Stem Cells; Urokinase receptor; Vascular Endothelial Growth Factor A - metabolism
• ISSN: 2157-6564; 2157-6580
• DOI: 10.5966/sctm.2013-0014

This study analyzed how patient age affected the angiogenic properties of adipose‐derived mesenchymal stromal cells (ADSCs). ADSCs from aged patients both with and without coronary artery disease 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. 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.