Role of FGF-2 Transfected Bone Marrow Mesenchymal Stem Cells in Engineered Bone Tissue for Repair of Avascular Necrosis of Femoral Head in Rabbits

Cell Physiol Biochem. 2018;48(2):773-784. doi: 10.1159/000491906. Epub 2018 Jul 19.

Abstract

Background/aims: Avascular necrosis of the femoral head (ANFH) is the focus and difficulty of orthopedic diseases. Recently, tissue engineering bone for this disease has shown a good therapeutic effect. The aim of the present study was to investigate the therapeutic effect of basic fibroblast growth factor (FGF-2) as cytokines transfected bone marrow mesenchymal stem cells (BMSCs) in constructing tissue-engineered bone for avascular necrosis of the femoral head.

Methods: The FGF-2 gene overexpressed lentivirus-transfected rBMSCs with xenogeneic antigen-extracted cancellous bone (XACB) to construct tissue engineered bone, and the model of early avascular necrosis of the femoral head was established by lipopolysaccharide (LPS) combined with hormone. The models were randomly divided into five groups: A (control), B (XACB), C (XACB+rBMSCs), D (XACB+rBMSCs+Lv-GFP), and E (XACB+rBMSCs+Lv-FGF-2/GFP) groups. The therapeutic effect of the tissue engineered bone for the avascular necrosis of the femoral head was evaluated by gross anatomy, X-ray examination, immunohistochemistry and H&E staining.

Results: The FGF-2 gene was transfected into rBMSCs (Multiplicity of infection [MOI] = 100) by lentivirus, and its efficiency was above 95%. The rBMSCs were successfully transfected overexpressing FGF-2 by qPCR and western blot. After tissue engineering bone implantation, X-ray examination and gross specimen observation revealed that the repair area in the E group was > 80% at six weeks, the defect was completely repaired at 12 weeks, and osteogenesis was stronger, when compared with the other groups. For the X-ray score, vascular area density and new bone formation area were higher, when compared with the other groups, and the difference was statistically significant (P< 0.05).

Conclusion: FGF-2 gene overexpression lentivirus transfection BMSCs combined with XACB to construct tissue engineered bone can effectively promote vascular regeneration, and improve the repair effect of avascular necrosis of the femoral head.

Keywords: Avascular necrosis of the femoral head; Basic fibroblast growth factor; Bone marrow mesenchymal stem cells; Tissue engineering bone.

MeSH terms

  • Animals
  • Bone Marrow Cells / cytology
  • Bone Regeneration / physiology
  • Bone and Bones / diagnostic imaging
  • Bone and Bones / pathology*
  • Cells, Cultured
  • Disease Models, Animal
  • Female
  • Femur Head Necrosis / etiology
  • Femur Head Necrosis / metabolism
  • Femur Head Necrosis / pathology*
  • Fibroblast Growth Factor 2 / genetics
  • Fibroblast Growth Factor 2 / metabolism*
  • Genetic Vectors / genetics
  • Genetic Vectors / metabolism
  • Lentivirus / genetics
  • Lipopolysaccharides / toxicity
  • Male
  • Mesenchymal Stem Cell Transplantation
  • Mesenchymal Stem Cells / cytology
  • Mesenchymal Stem Cells / metabolism
  • Osteogenesis
  • Rabbits
  • Tissue Engineering

Substances

  • Lipopolysaccharides
  • Fibroblast Growth Factor 2