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


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


BACKGROUND
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.
Minamide
Akihito
A
Department of Orthopaedic Surgery, Wakayama Medical University, Wakayama, Japan. minamide@wakayama-med.ac.
Yoshida
Munehito
M
Kawakami
Mamoru
M
Okada
Motohiro
M
Enyo
Yoshio
Y
Hashizume
Hiroshi
H
Boden
Scott D
SD
D000818:Animals; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins / Q000494:pharmacology*; D016025:Bone Transplantation; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology*; D005346:Fibroblast Growth Factors / Q000494:pharmacology*; D007085:Ilium / Q000166:cytology; D008159:Lumbar Vertebrae / Q000166:cytology / Q000000981:diagnostic imaging / Q000601:surgery*; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods*; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000187:drug effects*; D011183:Postoperative Complications / Q000401:mortality; D011817:Rabbits; D011859:Radiography; D011994:Recombinant Proteins / Q000494:pharmacology; D013123:Spinal Fusion / Q000379:methods*; D016212:Transforming Growth Factor beta / Q000494:pharmacology*
C525718:BMP2 protein, human; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins; D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta; D016222:Fibroblast Growth Factor 2; D005346:Fibroblast Growth Factors