Exogenous vascular endothelial growth factor delivery prior to endothelial precursor cell transplantation in orthotopic liver transplantation–induced hepatic ischemia/reperfusion injury

Abstract

Vascular endothelial growth factor (VEGF) promotes angiogenesis in vivo. We hypothesized that exogenous delivery of VEGF prior to bone marrow-derived endothelial precursor cell (EPC) transplantation may improve orthotopic liver transplantation (OLT)-induced hepatic ischemia/reperfusion injury (HIRI). OLT between Sprague Dawley donor rats and inbred LEW Wistar recipient rats was performed in 6 experimental groups to comparatively assess the effects of the VEGF gene: an untreated normal control group, a surgical control group, a liposomal control group, a VEGF group receiving only the liposome-encapsulated VEGF plasmid, an EPC group receiving only EPCs, and an EPC+VEGF group receiving the liposome-encapsulated VEGF plasmid followed by EPCs. VEGF plasmid delivery to liver tissue, endogenous VEGF, and vascular endothelial growth factor receptor (VEGFR) expression, liver transaminase levels, hepatocellular injury levels, apoptosis, apoptotic biomarkers, hepatotrophic mitogens, angiogenesis, and nitric oxide synthase (NOS) activity were assayed after OLT. Exogenous VEGF gene delivery prior to EPC transplantation significantly increased endogenous VEGF and VEGFR expression, significantly reduced liver transaminase levels, significantly reduced hepatocellular injury levels, significantly reduced hepatic apoptosis levels, and significantly reduced several apoptotic biomarkers (ie, B cell lymphoma 2-associated X protein/B cell lymphoma 2 ratio, caspase 3 activity, and heat shock protein 70 expression) in post-OLT-induced HIRI. Moreover, VEGF gene delivery prior to EPC transplantation significantly increased hepatotrophic mitogen expression (ie, epidermal growth factor, heparin-binding epidermal growth factor-like growth factor, hepatocyte growth factor, and transforming growth factor α), angiogenesis, and NOS activity in post-OLT-induced HIRI. In conclusion, exogenous liposomal delivery of the VEGF gene prior to bone marrow-derived EPC transplantation may be an effective strategy in decreasing OLT-induced HIRI. Liver Transplantation 23 804-812 2017 AASLD.

Exosomes Derived from Dendritic Cells Attenuate Liver Injury by Modulating the Balance of Treg and Th17 Cells After Ischemia Reperfusion

“…Many studies have demonstrated that the mechanism triggered by transplanted cells significantly contributes to liver IRI [31, 32]. Various proteins secreted by DCs play important roles in the improvement of liver function.…”

The Protective Effect of Panax notoginseng Mixture on Hepatic Ischemia/Reperfusion Injury in Mice via Regulating NR3C2, SRC, and GAPDH

“…DockThor online tool was used to carry out molecular docking of these target gene receptors and their corresponding small molecule conjugated ligands, and the results are shown in Table 2 . Cao et al (2017) recently reported that before bone marrow–derived endothelial progenitor cell transplantation, exogenous liposome delivery of VEGF gene may be an effective strategy to reduce orthotopic liver transplantation–induced HIRI. Jiao et al (2021) reported that VEGF and IL-6 play an important role in the study of the potential of mesenchymal stem cell secretome to promote liver regeneration after hepatic ischemia/reperfusion combined with partial resection.…”

Salvage of Unilateral Complete Ear Amputation with Continuous Local Hyperbaric Oxygen, Platelet-Rich Plasma and Polydeoxyribonucleotide without Micro-Revascularization

“…In the process of taking-up of composite grafts, inadequate tissue perfusion and ischemia-reperfusion injury are critical factors determining graft survival. The protective effect of VEGF on ischemia-reperfusion injury has been well established in transplantation surgery, such as kidney, lung and liver procedures [11][12][13], and those reports stated that VEGF affected endothelial cell survival, regulating their proliferation, regeneration, and apoptosis. Therefore, we expect that PDRN has the potential to improve the survival of composite grafts, enhancing neovascularization and protecting against ischemia-reperfusion injury by mediating an increase in VEGF.…”