Restoring Vasculogenic Potential of Endothelial Cells from Diabetic Patients Through Spheroid Formation

Introduction Diabetes is an emerging epidemic in the developing world and represents a major risk factor for cardiovascular disease. Among other issues, patients with diabetes suffer from diminished endothelial cell (EC) function, which contributes to impaired vasculogenesis and recovery from ischemic insult. The formation of cells into three-dimensional spheroids promotes cell survival and activates key signaling pathways through the upregulation of cell–cell contacts, providing an opportunity to overcome shortcomings associated with individual autologous cells. Methods We hypothesized that forming human microvascular endothelial cells (HMVECs) from diabetic patients into spheroids would restore their vasculogenic potential following upregulation of these cell–cell interactions. HMVEC spheroids were formed and suspended in fibrin gels to quantify vasculogenic potential. Results Individual HMVECs from diabetic patients exhibited similar proliferative and chemotactic potential to cells from healthy donors but reduced tubulogenesis. HMVEC spheroids formed from diabetic donors formed more sprouts than spheroids from healthy donors, and more sprouts than individual cells from either population. Compared to cells from healthy donors, sprout formation was more efficiently abrogated in HMVECs from diabetic patients by blocking matrix metalloproteinase activity. Conclusions This study demonstrates a promising approach for restoring the diminished vasculogenic potential of endothelial cells in diabetic patients.