BONE-FORMATION IN-VIVO - COMPARISON OF OSTEOGENESIS BY TRANSPLANTED MOUSE AND HUMAN MARROW STROMAL FIBROBLASTS

Background. Marrow stromal fibroblasts (MSFs) are known to contain bon e precursor cells. However, the osteogenic potential of human MSFs has been poorly characterized. The aim of this study was to compare the o steogenic capacity of mouse and human MSFs after implantation in vivo. Methods. After in vitro expansion, MSFs were loaded into a number of different vehicles and transplanted subcutaneously into immunodeficien t mice. Results. Mouse MSFs transplanted within gelatin, polyvinyl spo nges, and collagen matrices all formed a capsule of cortical-like bone surrounding a cavity with active hematopoiesis. In transplants of MSF s from transgenic mice harboring type I procollagen chloramphenicol ac etyltransferase constructs, chloramphenicol acetyltransferase activity was maintained for up to 14 weeks, indicating prolonged bone formatio n by transplanted MSFs. New bone formation by human MSFs was more depe ndent on both the in vitro expansion conditions and transplantation ve hicles. Within gelatin, woven bone was observed sporadically and only after culture in the presence of dexamethasone and L-ascorbic acid pho sphate magnesium salt n-hydrate. Consistent bone formation by human MS Fs was achieved only within vehicles containing hydroxyapatite/tricalc ium phosphate ceramics (HA/TCP) in the form of blocks, powder, and HA/ TCP powder-type I bovine fibrillar collagen strips, and bone was maint ained for at least 19 weeks. Cells of the new bone were positive for h uman osteonectin showing their donor origin. HA/TCP powder, the HA/TCP powder-type I bovine fibrillar collagen strips, and HA/TCP powder hel d together with fibrin were easier to load and supported more extensiv e osteogenesis than HA/TCP blocks and thus may be more applicable for therapeutic use. Conclusions. In this article, we describe the differe nces in the requirements for mouse and human MSFs to form bone, and re port the development of a methodology for the consistent in vivo gener ation of extensive bone from human MSFs.