The effects of bone morphogenetic protein and basic fibroblast growth factor on cultured mesenchymal stem cells for spine fusion

Spine (Phila Pa 1976). 2007 May 1;32(10):1067-71. doi: 10.1097/01.brs.0000261626.32999.8a.

Abstract

Study design: Posterolateral lumbar transverse process fusion was carried out using cultured mesenchymal stem cells with or without bone morphogenetic protein (BMP) and basic fibroblast growth factor (FGF).

Objectives: To determine the ability of BMP and basic FGF to enhance the efficacy of bone marrow-derived mesenchymal stem cells in lumbar arthrodesis.

Summary of background data: Our previous study hypothesized that it would be important to differentiate into osteogenic cells and to implant a large number of cells for achieving solid spinal fusions.

Methods: Thirty-six adult rabbits underwent single-level bilateral posterolateral intertransverse process fusions at L4-L5. Animals were divided into 5 groups, each according to the material implanted: (1) autologous bone (autograft; n = 8); (2) mesenchymal stem cells (n = 7); (3) mesenchymal stem cells with recombinant human bone morphogenetic protein (rhBMP)-2 (mesenchymal stem cell-BMP; n = 7); (4) mesenchymal stem cells with basic FGF (mesenchymal stem cell-FGF; n = 7); and (5) mesenchymal stem cells with rhBMP-2 and basic FGF (mesenchymal stem cell-BMP-FGF; n = 7). Fresh bone marrow cells from the iliac crest of each animal were cultured in a standard medium for 2 weeks. For an additional week, the mesenchymal stem cells (1 x 10(6) cells/mL) were cultured in 10(-8) M dexamethasone, type I collagen gel and porous hydroxyapatite particles with or without rhBMP-2 (2 microg/mL) and basic FGF (5 microg/mL). Animals were killed 6 weeks after surgery. Radiograph, manual palpation, and histology were used to evaluate spinal fusions.

Results: Fusion rates were 5/7 in the autograft group, 0/7 in the mesenchymal stem cell group, 2/7 in the mesenchymal stem cell-BMP group, 3/7 in the mesenchymal stem cell-FGF group, and 6/7 in the mesenchymal stem cell-BMP-FGF group. The histology in some of both mesenchymal stem cell-BMP and mesenchymal stem cell-FGF groups demonstrated that fibrous tissues and cartilages remained in grafted areas. In the mesenchymal stem cell-BMP-FGF group, each grafted fragment was connected with new bone ingrowths.

Conclusions: This study showed that bone marrow-derived mesenchymal stem cells cultured with rhBMP-2 and basic FGF act as a substitute for autograft in lumbar arthrodesis. This technique may yield a more consistent quality of fusion bone as compared to that with autograft.

Publication types

  • Comparative Study

MeSH terms

  • Animals
  • Bone Morphogenetic Protein 2
  • Bone Morphogenetic Proteins / pharmacology*
  • Bone Transplantation
  • Cell Differentiation / drug effects
  • Cell Division / drug effects
  • Cells, Cultured
  • Fibroblast Growth Factor 2 / pharmacology*
  • Fibroblast Growth Factors / pharmacology*
  • Ilium / cytology
  • Lumbar Vertebrae / cytology
  • Lumbar Vertebrae / diagnostic imaging
  • Lumbar Vertebrae / surgery*
  • Mesenchymal Stem Cell Transplantation / methods*
  • Mesenchymal Stem Cells / cytology
  • Mesenchymal Stem Cells / drug effects*
  • Postoperative Complications / mortality
  • Rabbits
  • Radiography
  • Recombinant Proteins / pharmacology
  • Spinal Fusion / methods*
  • Transforming Growth Factor beta / pharmacology*

Substances

  • BMP2 protein, human
  • Bone Morphogenetic Protein 2
  • Bone Morphogenetic Proteins
  • Recombinant Proteins
  • Transforming Growth Factor beta
  • Fibroblast Growth Factor 2
  • Fibroblast Growth Factors