Clinical Studies Of Osteogenic Cells

Dental &Craniofacial Research

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Linked publications & trials

Abstract

The Skeletal Clinical Studies program has established four clinical protocols (97-DK-0057, 98-D-0145, 98-D-0146, 99-D-003) for the study and treatment of fibrous dysplasia of bone (FD) and the McCune-Albright Syndrome (MAS). FD is found in a broad range of severity, ranging from monostotic (single bone) to polyostotic (many bones) and often in association with the MAS, which in addition to FD has multiple endocrinopathies and skin hyperpigmentation. FD is known to arise from a post-zygotic mutation in the GNAS1 gene (R201C and R201H). To date, 87 patients have been evaluated, and during the course of the natural history study, it was found that an approximately half of the patients have a renal phosphate wasting, which may further impact on the osteomalacic nature of FD lesions. Other generalized renal tubular dysfunction noted in these patients, such as abnormalities in vitamin D metabolism, proteinuria and aminoaciduria, suggest that fibrous dysplastic lesions produce a factor that impacts on renal function. Furthermore, two of the patients diagnosed else where were found not to have fibrous dysplasia, but other benign fibro-osseous diseases, emphasizing the need for genetic analysis for diagnosis. In addition, the program has continued to develop procedures whereby ex vivo expanded bone marrow stromal cells can be used in bone regeneration. The ex vivo expansions conditions were refined in order to avoid the use of fetal bovine serum prior to in vivo transplantation, and the optimal size and shape of the hydroxyapatite/tricalcium phosphate carrier particles was determined. These findings add necessary information for the successful clinical application of bone marrow stromal cell transplantation techniques in humans. Bone marrow stromal cells can also be used to create vascularized bone flaps in mice by wrapping the carrier containing the cells around an artery and vein, and further wrapping with Goretex to prevent collateral vascularization. Bone is formed within four weeks, and these bone constructs are vascularized by their pedicle and therefore can potentially be transferred to a recipient site using microsurgical techniques. These findings provide proof of principle of an additional clinical application of BMSC transplantation techniques.