Autologous bone marrow stromal cells loaded onto porous hydroxyapatite ceramic accelerate bone repair in critical-size defects of sheep long bones

The ability of marrow-derived osteoprogenitor cells to promote repair of cr itical-size tibial gaps upon autologous transplantation on a hydroxyapatite ceramic (HAC) carrier was tested ina sheep model,Conditions for in vitro e xpansion of sheep bone marrow stromal cells (BMSC) were established and the osteogenic potential of the expanded cells was validated. Ectopic implanta tion of sheep BMSC:in immunocompromised mice led to extensive bone formatio n. When used to repair tibial gays in sheep, cell-loaded implants (n = 2) c onducted a far more extensive bone formation than did cell-free E-IAC cylin ders (n = 2) over a 2-month period. In cell-loaded implants, bone formation was found to occur both within the internal macropore space and around the HAC cylinder while in control cell-free implants, bone formation was limit ed mostly to the outer surface and was not observed in most of the inner po res. As tested in an indentation assay, the stiffness of the complex MAC-bo ne material was found to be higher in cell-loaded implants compared to cont rols. Our Pilot study on a limited number of large-sized animals suggests t hat the use of autologous BMSC in conjunction with MAC-based carriers resul ts in faster bone repair compared to HAC alone. Potentially this combinatio n could be used clinically in the treatment of extensive long bone defects. (C) 2000 John Wiley & Sons, Inc.