Collagen-binding vascular endothelial growth factor (CBD-VEGF) promotes liver regeneration in murine partial hepatectomy

Liver regeneration is a complex process that needs orchestration of multiple nonparenchymal cells including sinusoid endothelial cells. Vascular endothelial growth factor (VEGF) serves a crucial role in angiogenesis and liver regeneration. However, the lack of an high-efficiency delivery system target to the injured site reduces the local therapeutic efficacy of VEGF. In our previous study, collagen binding VEGF (CBD-VEGF) was established by fusing collagen binding domain (CBD) into the N-terminal of native VEGF and improved cardiac function after myocardial infraction. The present study investigated the therapeutic effect of CBD-VEGF on liver regeneration by a mouse model of partial hepatectomy. After injection through portal vein following 2/3 hepatectomy, CBD-VEGF was largely retained in the hepatic extracellular matrix for 48 h. Furthermore, CBD-VEGF application significantly promoted sinusoidal regeneration and remodeling in remanent liver tissue 48 h after hepatectomy. In addition, CBD-VEGF treatment significantly enhanced the proliferation of hepatocytes at 2 and 3 days post-surgery compared with native VEGF, concomitant with attenuated liver injury. In conclusion, these results demonstrated that CBD-VEGF could be a promising therapeutic strategy for liver regeneration.