In vivo bone formation by human bone marrow cells: effect of osteogenic culture supplements and cell densities

Bone marrow is known to contain a population of osteoprogenitor cells that can go th rough complete differentiation when cultured in a medium containi ng appropriate bioactive factors. In this study, porous particles of a calc ium phosphate material were seeded with adult human bone marrow cells in th e second passage. After an additional culture period of 1 wk in the particl es, these hybrid constructs were subcutaneouslly implanted in nude mice wit h a survival period of 4 wk. The cell seeding densities range from 0-200 00 0 cells per particle and the cell culture system was designed to investigat e the single and combined effects of dexamethasone and recombinant human bo ne morphogenetic protein 2 (rhBMP-2). The hybrid "material/tissue" construc ts were processed for histology and the amount of de novo bone formation wa s quantified, for each culture condition, by histomorphometric techniques. The relative percentage of mineralized bone formation reached a maximal val ue of 19.77 +/- 5.06, for samples cultured in the presence of rhBMP-2 and w ith a seeding density of 200 000 cells/particle, compared to 0.52 +/- 0.45 for samples in which no cells had been cultured and had been incubated in c ulture medium supplemented with Dex and rhBMP-2. For the tested conditions a nd for the low cell numbers used in th is study, rhBMP-2 proved to be an essential bioactive factor to obtain in vivo bone formation by our culture system. The results from this study prove the potential of cultured adult h uman bone marrow cells to initiate and accelerate de novo bone formation af ter transplantation into an ectopic site. (C) 1998 Kluwer Academic Publishe rs.