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Differentiation Capacity of Human Aortic Perivascular Adipose Progenitor Cells
Published on: March 5, 2019
Endothelial differentiation of adipose-derived stem cells from elderly patients with cardiovascular disease
Ping Zhang1, Neil Moudgill, Eric Hager
1Department of Surgery, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA.
Insights
Adipose-derived stem cells (ASCs) from elderly patients effectively differentiate into endothelial cells. These cells show promise for vascular tissue engineering, as age does not hinder their therapeutic potential.
Area of Science:
- Regenerative Medicine
- Stem Cell Biology
- Vascular Biology
Background:
- Adipose-derived stem cells (ASCs) are crucial for tissue engineering.
- Investigating ASCs from elderly donors is vital for understanding age-related therapeutic potential.
Purpose of the Study:
- To assess the endothelial differentiation capacity of ASCs from elderly patients.
- To evaluate the functional attributes of these differentiated ASCs for vascular applications.
Main Methods:
- ASCs were isolated from 53 patients (aged 50-89).
- Cells were cultured in endothelial growth medium-2 and stimulated with VEGF and shear stress.
- Endothelial marker expression, functional assays, and PI(3)K pathway inhibition were analyzed.
- ASCs were tested on decellularized vein grafts under shear stress.
Main Results:
- Older donors yielded higher ASC numbers; age/comorbidity did not impede isolation.
- ASCs formed cords, exhibited endothelial markers (CD31, vWF), and uptook LDL.
- PI(3)K pathway inhibition blocked differentiation; shear stress enhanced anti-thrombogenic properties and integrin expression.
- Differentiated ASCs adhered strongly to basement membranes and resisted detachment on vein grafts.
Conclusions:
- ASCs from elderly individuals retain significant endothelial differentiation potential.
- Adipose tissue is a viable source of autologous stem cells for vascular tissue engineering across age groups.
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.

