Sustained vascular endothelial growth factor blockade by antivascular endothelial growth factor antibodies results in nonunion in the process of fracture healing in rabbits.

OBJECTIVE: To study the role of vascular endothelial growth factor (VEGF) in the process of fracture healing and the effect of VEGF and anti-VEGF polyclonal antibody on fracture healing. METHODS: One hundred and five New Zealand white rabbits were subjected to fracture of the middle part of the left radius, and were randomly divided into control, VEGF, and VEGF polyclonal antibody groups. The blood flow at the fracture site was measured by single photoemission computerized tomography after 8 hours, 24 hours, and 72 hours, and 1 weeks, 3 weeks, 5 weeks, and 8 weeks. X-ray films were taken after 1 weeks, 3 weeks, 5 weeks, and 8 weeks to observe the results of fracture healing. RESULTS: The blood flow at the fracture site in the VEGF group significantly increased compared with the control group during 8 hours to 1 week, but no obvious difference was seen on the X-ray films between the two groups. In the VEGF polyclonal antibody group, the blood flow at the fracture sites decreased significantly at all time points compared with the control group. The fracture healing process was disturbed, and nonunion signs were seen at the fracture site. CONCLUSIONS: The lack of VEGF may impede the fracture healing process, and results in nonunion at the fracture site.

Modification of the brain-derived neurotrophic factor gene: a portal to transform mesenchymal stem cells into advantageous engineering cells for neuroregeneration and neuroprotection.

Multipotential mesenchymal stem cells (MSCs) are ideal seed cells for recruiting the loss of neural cells due to their strong proliferative capacity, easy acquisition, and considerable tolerance of genetic modifications. After transduction of brain-derived neurotrophic factor (BDNF) gene via recombinant retroviral vectors into the human MSCs, nearly 100% of cells expressed BDNF (which were therefore transformed into BNDF-MSCs) as detected by immunocytochemistry, and the quantity of BDNF in the culture medium was increased by approximately 20,000-fold. In spite of the genomic integration of an exogenous gene, BDNF-MSCs did not present any structural aberration in the chromosomes. All-trans-retinoic acid (RA) induction caused the BDNF-MSCs to differentiate into neural cells with significantly increased expressions of such neural-specific proteins as nestin, NeuN, O4, and glial fibrillary acidic protein (GFAP). The voltage-dependent K+/Ca2+ currents were recorded from the induced BDNF-MSCs using patch-clamp technique. Compared with the MSCs induced by both RA and BDNF, BDNF-MSCs survived in significantly greater number in the induction medium, and also more cells were induced into neuron-like cells (NeuN, P < 0.01) and oligodendrocyte-like cells (O4, P < 0.05). We suppose that, once engrafted into human central nervous system, the BDNF-MSCs would not only recruit the neuronal losses, but also provide, by way of paracrine, large quantities of BDNF that effectively perform the functions of neuroprotection and neuroregeneration, promoting the activation of endogenous neural stem/progenitor cells and their chemotactic migration. On the other hand, the BDNF-MSCs that can survive in the host environment and differentiate subsequently into functional mature cells may also serve as specifically targeting vectors for ex vivo gene therapy.

[Effect of vascular endothelial growth factor in fracture healing].

OBJECTIVE: To observe the effect of vascular endothelial growth factor (VEGF) in fracture healing and to investigate the influence of VEGF and VEGF antibody in fracture healing. METHODS: One hundred and five rabbits were used to make fracture model in the left radius and randomly divided into control group, VEGF group and VEGF antibody group. VEGF and VEGF antibody were used in the VEGF group and VEGF antibody group respectively, then the blood flow of the fracture ends was measured by single photon emission computed tomography (SPECT) 8, 24, 72 hours, 1, 3, 5 and 8 weeks after fracture, the X-ray films of the fracture sites were taken after 1, 3, 5 and 8 weeks to observe the fracture healing. RESULTS: The blood flow of the fracture ends in the VEGF group increased during a period from 8 h to 3 wk after fraction when compared with that of the control group, and no obvious difference was seen on the X-ray films between the two groups. In the VEGF antibody group, the blood flow of the fracture ends decreased obviously when compared with that of the control group. The fracture healing process was interfered seriously and nonunion change was seen in the fracture site. CONCLUSION: The lack of VEGF will interfere with the fracture healing process and result in nonunion in the fracture site. Administration of ectogenous VEGF may promote fracture healing by increasing the blood flow of the fracture ends.