Mesenchymal stem cells reside in bone marrow and, when these cells are inco
rporated into porous ceramics, the composites exhibit osteo-chondrogenic ph
enotypic expression in ectopic (subcutaneous and intramuscular) or orthotop
ic sites. The expressional cascade is dependent upon the material propertie
s of the delivery vehicle. Bioactive ceramics provide a suitable substrate
for the attachment of the cells. This is followed by osteogenic differentia
tion directly on the surface of the ceramic, which results in bone bonding.
Nonbioactive materials show neither surface-dependent cell differentiation
nor bone bonding, The number of mesenchymal stem cells in fresh adult bone
marrow is small, about one per one-hundred-thousand nucleated cells, and d
ecreases with donor age. Irt vitro cell culture technology can be used to m
itotically expand these cells without the loss of their developmental poten
cy regardless of donor age. The implanted composite of porous ceramic and c
ulture-expanded mesenchymal stem cells exhibits in vivo osteo-chondrogenic
differentiation. In certain culture conditions, these stem cells differenti
ate into osteoblasts, which make bone matrix on the ceramic surface. Such i
n vitro prefabricated bone within the ceramic provides immediate new bone-f
orming capability after bl vivo implantation. Prior to loading of the cultu
red, marrow-derived mesenchymal stem cells into the porous ceramics, exogen
ous genes can be introduced into these cells in culture. Combining in vitro
manipulated mesenchymal stem cells with porous ceramics can be expected to
effect sufficient new bone-forming capability, which can thereby provide t
issue engineering approaches to patients with skeletal defects in order to
regenerate skeletal tissues. (C) 1999 John Wiley & Sons, Inc.