title: Endothelial differentiation of adipose-derived stem cells from elderly patients with cardiovascular disease.
abstract: Adipose-derived stem cells (ASCs) possess significant therapeutic potential for tissue engineering and regeneration. This study investigates the endothelial differentiation and functional capacity of ASCs isolated from elderly patients. Isolation of ASCs from 53 patients (50-89 years) revealed that advanced age or comorbidity did not negatively impact stem cell harvest; rather, higher numbers were observed in older donors (>70 years) than in younger. ASCs cultured in endothelial growth medium-2 for up to 3 weeks formed cords upon Matrigel and demonstrated acetylated-low-density lipoprotein and lectin uptake. Further stimulation with vascular endothelial growth factor and shear stress upregulated endothelial cell-specific markers (CD31, von Willebrand factor, endothelial nitric oxide synthase, and VE-cadherin). Inhibition of the PI(3)K but not mitogen-activated protein kinase pathway blocked the observed endothelial differentiation. Shear stress promoted an anti-thrombogenic phenotype as demonstrated by production of tissue-plasminogen activator and nitric oxide, and inhibition of plasminogen activator inhibitor-1. Shear stress augmented integrin α(5)β(1) expression and subsequently increased attachment of differentiated ASCs to basement membrane components. Finally, ASCs seeded onto a decellularized vein graft resisted detachment despite application of shear force up to 9 dynes. These results suggest that (1) advanced age and comorbidity do not negatively impact isolation of ASCs, and (2) these stem cells retain significant capacity to acquire key endothelial cell traits throughout life. As such, adipose tissue is a practical source of autologous stem cells for vascular tissue engineering.
authors.affiliation: Department of Surgery, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA.
authors.forename: Ping
authors.initials: P
authors.lastname: Zhang
authors.forename: Neil
authors.initials: N
authors.lastname: Moudgill
authors.forename: Eric
authors.initials: E
authors.lastname: Hager
authors.forename: Nicolas
authors.initials: N
authors.lastname: Tarola
authors.forename: Christopher
authors.initials: C
authors.lastname: Dimatteo
authors.forename: Stephen
authors.initials: S
authors.lastname: McIlhenny
authors.forename: Thomas
authors.initials: T
authors.lastname: Tulenko
authors.forename: Paul J
authors.initials: PJ
authors.lastname: DiMuzio
mesh_terms: D000273:Adipose Tissue / Q000166:cytology*; D000368:Aged; D000369:Aged, 80 and over; D058833:Antithrombin Proteins / Q000378:metabolism; D001485:Basement Membrane / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism; D001808:Blood Vessels / Q000378:metabolism; D002318:Cardiovascular Diseases / Q000473:pathology*; D002448:Cell Adhesion; D002454:Cell Differentiation; D002462:Cell Membrane / Q000378:metabolism; D002469:Cell Separation; D042783:Endothelial Cells / Q000166:cytology*; D006801:Humans; D016130:Immunophenotyping; D008875:Middle Aged; D039902:Multipotent Stem Cells / Q000166:cytology; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D000081082:Phosphoinositide-3 Kinase Inhibitors; D013234:Stem Cells / Q000166:cytology* / Q000201:enzymology; D013314:Stress, Mechanical; D015854:Up-Regulation
chemical_list: D058833:Antithrombin Proteins; D015415:Biomarkers; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors