Lumbar interbody fusion using autologous bone marrow mesenchymal stem cell-calcium phosphate ceramic composite in rhesus monkey

Abstract

To determine the osteogenic capacity of autologous bone marrow mesenchymal stem cells (BMSCs)-calcium phosphate ceramic composites in vitro and implanted as a bone graft substitute for lumbar anterior interbody fusion in rhesus monkeys. From March 2003 to April 2005, 9 adult rhesus monkeys underwent lumbar L(3 - 4) and L(5 - 6) discectomy and interbody fusion via an anterior retroperitoneal approach. Two fusion sites in each animal were randomly assigned to two of three treatments: autogenous tricortical iliac crest bone graft (autograft group, n = 6) or cell-free ceramic graft (ceramic group, n = 6) or BMSCs-ceramic composite graft (BMSCs group, n = 6). Autologous BMSCs were culture-expanded and stimulated with osteogenic supplement. The cell-ceramic composites were constructed in a rotary dynamic cell culture system. The spinal fusion segments were evaluated by radiography, biomechanical testing, histologic analysis and histomorphometric analysis at 3 months post-surgery. Biomechanical testing showed that spinal segments from the autograft group and the BMSCs-ceramic group were statistically and significantly stiffer than the cell-free ceramic group. The BMSCs-ceramic group and the autograft group showed equivalent biomechanical stiffness by statistical analysis. Histologically, both the autograft group and the BMSCs-ceramic group achieved osseous union, but the cell-free ceramic group had a fibrous union. Quantitative histologic analysis showed that the amount of bone formation was significantly greater in the autograft group and the BMSCs-ceramic group compared with the cell-free ceramic group. However, the amount of ceramic residue was significantly greater in the cell-free ceramic group versus the BMSCs-ceramic group. The results indicate that BMSC-ceramic composites can enhance bone regeneration and achieve osseous spinal fusion 3 months after the implantation in rhesus monkey interbody fusion model. Cell-free ceramics has an unsatisfactory efficacy in spinal fusion due to its tense fibrous fusion.