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(American Journal of Pathology. 2006;168:542-550.)
© 2006 American Society for Investigative Pathology

Canine Cranial Reconstruction Using Autologous Bone Marrow Stromal Cells

Mahesh H. Mankani*, Sergei A. Kuznetsov{dagger}, Brian Shannon{dagger}, Ravi K. Nalla{ddagger}, Robert O. Ritchie{ddagger}, Yixian Qin§ and Pamela Gehron Robey{dagger}

From the Department of Surgery,* Division of Plastic Surgery, University of California, San Francisco, San Francisco, California; the Craniofacial and Skeletal Diseases Branch,{dagger} National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, Maryland; the Materials Sciences Division,{ddagger} Lawrence Berkeley National Laboratory, and Department of Materials Science and Engineering, University of California, Berkeley, Berkeley, California; and the Department of Biomedical Engineering,§ State University of New York at Stony Brook, Stony Brook, New York

Limited-sized transplants of culture-expanded autologous or allogeneic bone marrow stromal cells (BMSCs) form cortico-cancellous bone in rodent models. Initiation of clinical studies using autologous BMSC transplantation requires effective bone formation among sizable transplants in a large animal model as well as noninvasive techniques for evaluating transplant success. Here, we obtained bone marrow from the femurs of six dogs and expanded BMSCs in tissue culture. Autologous BMSC-hydroxyapatite/tricalcium phosphate (HA/TCP) transplants were introduced into critical-sized calvarial defects and contralateral control skull defects received HA/TCP vehicle alone. At intervals ranging from 2 to 20 months, transplants were biopsied or harvested for histological and mechanical analysis. Noninvasive studies, including quantitative computed tomography scans and ultrasound, were simultaneously obtained. In all animals, BMSC-containing transplants formed significantly more bone than their control counterparts. BMSC-associated bone possessed mechanical properties similar to the adjacent normal bone, confirmed by both ultrasound and ex vivo analysis. Evaluation by quantitative computed tomography confirmed that the extent of bone formation demonstrated by histology could be discerned through noninvasive means. These results show that autologous cultured BMSC transplantation is a feasible therapy in clinical-sized bone defects and that such transplants can be assessed noninvasively, suggesting that this technique has potential for use in patients with certain bone defects.




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Copyright © 2006 by the American Society for Investigative Pathology.