Pedicled bone flap formation using transplanted bone marrow stromal cells

Hypothesis: Transplanted osteoprogenitor cells derived from cultured bone m arrow stromal cells (BMSCs) can be used to fabricate pedicled bone flaps. Design: Prospective, randomized experimental trials. Setting: Basic science research laboratory. Materials: Immunodeficient female NIH-Bg-Nu-Xid mice, aged 3 months. Intervention: The BMSCs were harvested from the long bones of C57B1/6 trans genic mice carrying the type I alpha (1) collagen-chloramphenicol acetyl tr ansferase reporter gene construct; their numbers were expanded in tissue cu lture. Treated mice received BMSC transplantations around the common caroti d artery and internal jugular vein, the aorta and its venae comitantes, or the saphenous artery and vein; control mice received a sham transplant in c omparable recipient sites. Main Outcome Measures: Mice underwent harvesting from 4 weeks to 2 years af ter transplantation. Transplants were evaluated via histological, immunohis tochemical, and angiographic analyses. Results: Compared with the controls, which formed no bone, 32 of 37 BMSC-co ntaining transplants formed a vascularized bone island that was perfused sp ecifically and solely by its common carotid artery vascular source. Mature transplants consisted of well-developed lamellar, corticocancellous bone wh ose osteocytes were derived from the grafted BMSCs; hematopoietic tissue de rived from the recipient mouse. Transplants formed as early as 4 weeks and remained stable in size as late as 108 weeks. Conclusions: Bone marrow stromal cells can be used to create vascularized b one flaps in mice; these bone constructs are vascularized by their pedicle and therefore can potentially be transferred to a recipient site using micr osurgical techniques. These findings provide proof of principle of an addit ional clinical application of BMSC transplantation techniques.