Exogenous VEGF-C Augments the Efficacy of Therapeutic Lymphangiogenesis Induced by Allogenic Bone Marrow Stromal Cells in a Rabbit Model of Limb Secondary Lymphedema

OBJECTIVE: To determine the effect of bone marrow stromal cells transplantation and vascular endothelial growth factor C administration as a treatment for secondary lymphedema. METHODS: Bone marrow stromal cells and/or vascular endothelial growth factor C protein were injected into a rabbit model of limb lymphedema. Water displacement volumetry was performed to measure limb volume changes. Immunohistochemistry was performed to detect VEGFR-3 and to count lymph vessel. Western blot analysis was performed to detect vascular endothelial growth factor C. RESULTS: Before treatment, rabbits had an average volume of edema in the limb of 61.25 ± 5.28, 62.37 ± 4.97, 60.58 ± 7.18 and 61.79 ± 4.33 ml (P = 0.753), respectively, in the BMSC + VEGF-C, bone marrow stromal cell, vascular endothelial growth factor C and control groups. With therapy, this was reduced to an average volume of 7.60 ± 3.02, 12.78 ± 3.41, 31.55 ± 3.51 and 62.33 ± 6.59 ml, respectively, in the four groups 6 months after treatment. Quantitative analysis showed that the vessel numbers were significantly increased in the BMSC + VEGF-C, bone marrow stromal cell and vascular endothelial growth factor C groups compared with the control group at 28 days after the operation (P< 0.05). Western blot analysis demonstrated that expression of vascular endothelial growth factor C was higher in the BMSC + VEGF-C and BMSC groups. CONCLUSIONS: The combined treatment with bone marrow stromal cell transplantation and vascular endothelial growth factor C administration is superior to bone marrow stromal cell transplantation alone in the treatment of limb lymphedema. Bone marrow stromal cell transplantation and vascular endothelial growth factor C administration could enhance the therapeutic effect of each other.