Bone formation using novel interconnected porous calcium hydroxyapatite ceramic hybridized with cultured marrow stromal stem cells derived from Green rat.

The clinical use of cultured marrow stromal stem cells (MSCs) has recently attracted attention in the field of tissue engineering. For the clinical use of the MSCs, a prominent scaffold is needed. A scaffold hybridized with MSCs is transformed into a "bioactive bone substitute," and this provides good osteoconduction. In this study, a novel calcium hydroxyapatite ceramic with an interconnected porous structure (IP-CHA) was used as a scaffold. MSCs were harvested from Green rats containing Green Fluorescent Protein (GFP), and then these hybrids were implanted into the tibias of Sprague-Dawley rats. The purposes of this study were to examine the osteogenic ability of these hybrids without coculture, and to evaluate whether the resulting bone formation originated from the grafted MSCs or the recipient's cells. The hybridized group showed excellent bone formation compared with the IP-CHA-only implant group. Observation of the implanted MSCs revealed that they survived 8 weeks after surgery, and differentiated into osteoblast-like cells, thus providing bone formation. This implantation of the MSCs/IP-CHA composite provides excellent osteoconduction, and is expected to have extensive clinical applications.

[1]  C. Maniatopoulos,et al.  Bone formation in vitro by stromal cells obtained from bone marrow of young adult rats , 1988, Cell and Tissue Research.

[2]  H. Yoshikawa,et al.  Novel hydroxyapatite ceramics with an interconnective porous structure exhibit superior osteoconduction in vivo. , 2002, Journal of biomedical materials research.

[3]  A. Caplan Mesenchymal stem cells and gene therapy. , 2000, Clinical orthopaedics and related research.

[4]  M. Pittenger,et al.  Human mesenchymal stem cells: progenitor cells for cartilage, bone, fat and stroma. , 2000, Current topics in microbiology and immunology.

[5]  C. Rey,et al.  Osteoclast adhesion and activity on synthetic hydroxyapatite, carbonated hydroxyapatite, and natural calcium carbonate: relationship to surface energies. , 1999, Journal of biomedical materials research.

[6]  M. Pittenger,et al.  Multilineage potential of adult human mesenchymal stem cells. , 1999, Science.

[7]  S. Simske,et al.  Long-term bone ingrowth and residual microhardness of porous block hydroxyapatite implants in humans. , 1998, Journal of oral and maxillofacial surgery : official journal of the American Association of Oral and Maxillofacial Surgeons.

[8]  H. Oonishi,et al.  Hydroxyapatite in revision of total hip replacements with massive acetabular defects: 4- to 10-year clinical results. , 1997, The Journal of bone and joint surgery. British volume.

[9]  S. Radin,et al.  Effect of bioactive ceramic composition and structure on in vitro behavior. III. Porous versus dense ceramics. , 1994, Journal of biomedical materials research.

[10]  C. V. van Blitterswijk,et al.  Hydroxylapatite/poly(L-lactide) composites: an animal study on push-out strengths and interface histology. , 1993, Journal of biomedical materials research.

[11]  Arnold I. Caplan,et al.  Mesenchymal Stem Cells , 1991, Journal of orthopaedic research : official publication of the Orthopaedic Research Society.

[12]  H. Ohgushi,et al.  Bonding osteogenesis in coralline hydroxyapatite combined with bone marrow cells. , 1991, Biomaterials.

[13]  V. Goldberg,et al.  Osteogenic potential of culture-expanded rat marrow cells as assayed in vivo with porous calcium phosphate ceramic. , 1991, Biomaterials.

[14]  S Tamai,et al.  Marrow cell induced osteogenesis in porous hydroxyapatite and tricalcium phosphate: a comparative histomorphometric study of ectopic bone formation. , 1990, Journal of biomedical materials research.

[15]  H. Ohgushi,et al.  Osteogenic capacity of rat and human marrow cells in porous ceramics. Experiments in athymic (nude) mice. , 1990, Acta orthopaedica Scandinavica.

[16]  V. Goldberg,et al.  Heterotopic osteogenesis in porous ceramics induced by marrow cells , 1989, Journal of orthopaedic research : official publication of the Orthopaedic Research Society.

[17]  R. Holmes,et al.  Hydroxyapatite and tricalcium phosphate bone graft substitutes. , 1987, The Orthopedic clinics of North America.

[18]  S F Hulbert,et al.  Tissue reaction to three ceramics of porous and non-porous structures. , 1972, Journal of biomedical materials research.