VEGF165 gene-modified human umbilical cord blood mesenchymal stem cells protect against acute liver failure in rats.

Abstract

Human umbilical cord blood mesenchymal stem cells (HUCB-MSCs) can exert a protective effect in rat models of acute liver failure (ALF). Vascular endothelial growth factor 165 (VEGF165 ) is the predominant VEGF isoform and possesses a strong pro-angiogenic function. In the present study, HUCB-MSC served as the gene delivery vehicle for the VEGF165 gene, and we explored the therapeutic effects of this system on ALF. HUCB-MSCs were infected with an adenovirus expressing green fluorescent protein (GFP)-VEFG fusion protein (Ad-VEGF165 ) to overexpress VEGF165 or an adenovirus expressing GFP (Ad-GFP) as control. The control and modified HUCB-MSCs were then transplanted into ALF model rats. Liver function and liver pathological changes were assessed by biochemical tests and liver histology. Immunohistochemistry was carried out to determine the expression of, CD34, Ki67 and VEGF. VEGF165 overexpression enhanced the multipotency of HUCB-MSCs and promoted the homing and colonization of HUCB-MSC in the liver tissues of ALF rats. Furthermore, although HUCB-MSC transplantation ameliorated liver damage and promoted liver regeneration to some extent in ALF rats, Ad-VEGF165 -HUCB-MSC transplantation showed stronger therapeutic effects on ALF. In summary, transplantation of VEGF165 -modified HUCB-MSCs exert stronger therapeutic effects on ALF than HUCB-MSCs. The present study provides a novel therapeutic approach for ALF.