title: Exogenous VEGF-C augments the efficacy of therapeutic lymphangiogenesis induced by allogenic bone marrow stromal cells in a rabbit model of limb secondary lymphedema.
abstract: 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.
authors.affiliation: Department of Vascular Surgery, Shandong Provincial Hospital, Shandong University, 324 Jingwu Road, Jinan 250021, Shandong Province, China.
authors.forename: Hua
authors.initials: H
authors.lastname: Zhou
authors.forename: Mo
authors.initials: M
authors.lastname: Wang
authors.forename: Chuanqiang
authors.initials: C
authors.lastname: Hou
authors.forename: Xing
authors.initials: X
authors.lastname: Jin
authors.forename: Xuejun
authors.initials: X
authors.lastname: Wu
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D015153:Blotting, Western; D016026:Bone Marrow Transplantation; D003131:Combined Modality Therapy; D004195:Disease Models, Animal; D005240:Feasibility Studies; D006614:Hindlimb; D007150:Immunohistochemistry; D042583:Lymphangiogenesis; D042601:Lymphatic Vessels / Q000378:metabolism / Q000473:pathology; D008209:Lymphedema / Q000188:drug therapy* / Q000209:etiology / Q000601:surgery*; D011817:Rabbits; D014184:Transplantation, Homologous; D042582:Vascular Endothelial Growth Factor C / Q000008:administration & dosage / Q000302:isolation & purification / Q000494:pharmacology*; D040321:Vascular Endothelial Growth Factor Receptor-3 / Q000302:isolation & purification
chemical_list: D042582:Vascular Endothelial Growth Factor C; D040321:Vascular Endothelial Growth Factor Receptor-3