Although a number of studies have examined the fate of graft-derived cells
during the process of fusion, there remains no consensus regarding their ex
act 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 o
f syngeneic female hosts. Both models were characterized histologically and
histochemically. Graft-derived cells were then identified by fluorescent i
n 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 s
ite. The predominant graft-derived cell types included chondrocytes, osteob
lasts, and fibroblasts. Chondrocytes arose from precursor cells in the graf
t 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 ce
lls 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 corti
cal 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 ear
ly phases.