Transplanted bone marrow cells localize to fracture callus in a mouse model.
Bone marrow contains many cellular elements that may contribute to fracture repair. We used a pluripotential stromal cell in a mouse model to demonstrate the presence of transplanted cells in fracture hematoma and subsequently in maturing fracture callus. Cells were transduced with traceable genes (lac Z and neomycin resistance) and traced in vivo after intravenous injection into syngeneic mice. These transduced cells home to bone marrow, suggesting that they might be detected in fracture callus. Cells were injected intravenously into mice and stabilized femoral shaft fractures were induced. Control mice received intravenous lactated-Ringer's solution prior to fracture. Callus tissue and marrow were examined histologically from I to 10 weeks after fracture to detect transplanted cells. Transplanted cells were detected in fracture callus in areas, and at times, of most active bone formation. Control specimens showed minimal staining of the callus tissue. Levels of the traceable gene in fracture callus increased, reached a peak between 3 and 4 weeks after fracture, then diminished and disappeared by 10 weeks post-fracture as woven bone at the fracture site was replaced by lamellar bone with cells from the host mouse. The results show that pluripotent bone marrow cells home to the marrow after systemic injection and localize in fracture callus.
Devine
Michael J
MJ
Departments of Orthopaedics, School of Medicine, University of Virginia, Box 800374, Charlottesville, VA 22908, USA.
Mierisch
Cay M
CM
Jang
Euichan
E
Anderson
Peggy C
PC
Balian
Gary
G
D000818:Animals; D016026:Bone Marrow Transplantation; D002146:Bony Callus / Q000166:cytology*; D005264:Femoral Fractures / Q000503:physiopathology* / Q000628:therapy; D017930:Genes, Reporter; D007763:Lac Operon; D051379:Mice; D008807:Mice, Inbred BALB C; D023421:Models, Animal; D039904:Pluripotent Stem Cells / Q000637:transplantation; D017154:Stromal Cells / Q000637:transplantation