Adipose-Derived Stem Cells Can Contribute to Vascular Network Formation in Poly(ethylene Glycol) Hydrogel Scaffolds

Abstract

Although adipose-derived stem cells (ADSCs) can influence wound healing, their role in neovascularization is unclear. Utilizing three-dimensional in vitro, we sought to determine whether ADSCs cultured under varying conditions could contribute to vascular network formation, functioning as either endothelial cells (ECs) or supporting pericytes.. To study this, ADSCs were encapsulated in 3D hydrogels either with human brain vascular pericytes (HBVP, to show ADSC functions as ECs) or with human umbilical vein endothelial cells (HUVEC, to show ADSC functions as pericytes). The hydrogel used provides a 3D cell-adhesive, proteolytically degradable cell culture matrix that supports formation of vascular networks by encapsulated endothelial cells and pericytes. For this study, ADSCs were cultured in either basal media (basal) or EGM-2 media with 20 ng/mL of VEGF (stimulated) for 7 days and then encapsulated with HUVECs or HBVPs. When encapsulated with HBVPs, both basal and stimulated ADSCs were capable of forming CD31+ tubule-like networks, indicating endothelial function. In co-culture with HUVECs, basal and stimulated ADSCs were capable of enhancing and stabilizing formation of CD31+ tubule-like networks by the HUVECs and localized along the outer surfaces of the endothelial tubules, indicating pericyte-like function. These studies were repeated with diabetic ADSCs to examine the influence of this phenotype on the cells’ ability to influence neovascularization. Both basal and stimulated diabetic ADSCs were capable of supporting tubule formation by HUVECs, though to a lesser degree than non-diabetic ADSCs. Notably, diabetic ADSCs were not capable of forming CD31+ tubules when co-cultured with HBVPs, indicating loss of endothelial function. Adipose-derived stem cells (ADSCs) are known to play a role in wound healing; however, the exact role of these cells in neovascularization is unclear. Our work focuses on understanding specific cell–cell interactions between ADSCs, endothelial cells, and mesenchymal support cells within a 3D poly(ethylene glycol) hydrogel scaffold. Furthermore, we sought to understand the effect of the diabetic phenotype on this phenomenon as well.