Stem cell technology and bioceramics: From cell to gene engineering

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.