A simplified in vitro disease-mimicking culture system can determine the angiogenic effect of medicines on vascular diseases.

Abstract

Many patients undergoing clinical regenerative treatments experience severe conditions arising from endothelial disruption. In chronic cardiac and perivascular diseases, deficiencies in vascular endothelial growth factor (VEGF), insulin-like growth factor (IGF), and heparin, which are essential for maintaining and activating endothelial cells, can lead to angiogenic dysregulation. Endothelial disruption caused by ischemic hypoxia and a deficiency in these factors is associated with many vascular diseases. However, their pathogenic processes remain unclear at the cellular level. Therefore, the present study aimed to develop a culture system that mimics the disease environment to test the effectiveness of drug candidates in restoring damaged blood vessels in chronic vascular diseases, including coronary artery disease and peripheral vascular disease. This study focused on VEGF, IGF, and heparin and developed a pseudo-disease culture system by pre-treating human umbilical vein endothelial cells (HUVECs) with a starvation medium (EGM-2™ medium lacking VEGF, IGF, and heparin) to examine the ability of HUVECs to form a traditional 2D vascular network. The results indicated that a deficiency in these proteins results in disruptions in tube morphogenesis. Moreover, the results suggested that dysregulation of the PI3K/AKT pathway plays a key role for in vascular disruption in HUVECs. The proposed pseudo-disease starvation system provides a simple way to visualize pathological disruptions to blood vessels and assess the efficacy of drugs for vascular regeneration.

Supplementary information: The online version contains supplementary material available at 10.1007/s10616-025-00736-4.