Repair of craniotomy defects using bone marrow stromal cells

Background. Techniques used to repair craniofacial skeletal defects paralle l the accepted surgical therapies for bone lass elsewhere in the skeleton a nd include the use of autogenous bone and alloplastic materials. Transplant ation of a bone marrow stromal cell population that contains osteogenic pro genitor cells may be an additional modality for the generation of new bone. Methods. Full thickness osseous defects (5 mm) were prepared in the cranium of immunocompromised mice and were treated with gelatin sponges containing murine alloplastic bone marrow stromal cells derived from transgenic mice carrying a type I collagen-chloramphenicol acetyltransferase reporter gene to follow the fate of the transplanted cells. Control surgical sites were t reated with spleen stromal cells or gelatin sponges alone, or were left unt reated. The surgical defects were analyzed histologically for percent closu re of the defect al 2, 3, 4, 6, and 12 weeks. Results. Cultured bone marrow stromal cells transplanted within gelatin spo nges resulted in osteogenesis that repaired greater than 99.0+/-2.20% of th e original surgical defect within 2 weeks. In contrast, cranial defects tre ated with splenic fibroblasts, vehicle alone,, or sham-operated controls re sulted in minimal repair that was limited lo the surgical margins, Bone mar row stromal cells carrying the collagen transgene were immunodetected only in the newly formed bone and thus confirmed the donor origin of the transpl anted cells. Conclusions. These studies demonstrate that mitotically expanded bone marro w cells can serve as an abundant source of osteoprogenitor cells that are c apable of repairing craniofacial skeletal defects in mice without the addit ion of growth or morphogenetic factors.