Cellular contribution of bone graft to fusion

Abstract

Although a number of studies have examined the fate of graft-derived cells during the process of fusion, there remains no consensus regarding their exact contribution to bone formation within the fusion mass. We developed two chimeric mouse isograft fusion models that allowed us to track the fate of graft cells within the host fusion bed. Cortical/cancellous bone graft (1:1 ratio of pelvic to vertebral body bone) from male mice was placed between (a) the tibia and fibula or (b) the coccygeal spine transverse processes of syngeneic female hosts. Both models were characterized histologically and histochemically. Graft-derived cells were then identified by fluorescent in situ hybridization for Y-chromosome sequences present in only the graft (male) cells. When the fusion mass was healing but not yet fused (at 1 and 2 weeks), numerous graft-derived cells were observed throughout the fusion site. The predominant graft-derived cell types included chondrocytes, osteoblasts, and fibroblasts. Chondrocytes arose from precursor cells in the graft de novo. as cartilage was not transplanted during the surgical procedure. By the time a mature fusion mass had formed (at 6 weeks), graft-derived cells persisted as osteocytes within the cortical rim surrounding the fusion mass. These osteocytes likely differentiated from graft-derived precursors that had directly formed bone, because transplanted osteocytes within cortical bone graft fragments were noted to rarely survive even at 1 and 2 weeks. Collectively, our results demonstrate for the first time that bone graft contributes cells that, in conjunction with host cells, directly form bone within the fusion mass during all phases of fusion rather than just the early phases.