In Vivo Bone Formation by Human Bone Marrow Stromal Cells: Reconstruction of the Mouse Calvarium and Mandible

Bone marrow stromal cells (BMSCs) contain a subset of multipotent cells with the potential to repair hard‐tissue defects. Mouse BMSCs, combined with a collagen carrier, can close critical‐sized homologous mouse calvarial defects, but this new bone has a poor union with the adjacent calvarium. When h...

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Bibliographic Details
Published in:Stem cells (Dayton, Ohio) Ohio), 2006-09, Vol.24 (9), p.2140-2149
Main Authors: Mankani, Mahesh H., Kuznetsov, Sergei A., Wolfe, Raymond M., Marshall, Grayson W., Robey, Pamela Gehron
Format: Article
Language:English
Subjects:
Animals
Bone Marrow Cells - cytology
Bone marrow stromal cells
Bone Marrow Transplantation
Cells, Cultured
Cellular therapy
Culture
Female
Humans
Long‐term engraftment
Long‐term survival
Mandible - cytology
Mice
Osteogenesis - physiology
Osteoprogenitor
Skull - cytology
Stromal Cells - cytology
Time Factors
Xenogeneic stem cell transplantation
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Summary:Bone marrow stromal cells (BMSCs) contain a subset of multipotent cells with the potential to repair hard‐tissue defects. Mouse BMSCs, combined with a collagen carrier, can close critical‐sized homologous mouse calvarial defects, but this new bone has a poor union with the adjacent calvarium. When human BMSCs are transplanted for the purpose of engineering new bone, best results can be achieved if the cells are combined with hydroxyapatite/tricalcium phosphate (HA/TCP) particles. Here, we demonstrate that transplantation of cultured human BMSCs in conjunction with HA/TCP particles can be used successfully to close mouse craniofacial bone defects and that removal of the periosteum from the calvarium significantly enhances union with the transplant. Transplants were followed for up to 96 weeks and were found to change in morphology but not bone content after 8 weeks; this constitutes the first description of human BMSCs placed long‐term to heal bone defects. New bone formation continued to occur in the oldest transplants, confirmed by tetracycline labeling. Additionally, the elastic modulus of this engineered bone resembled that of the normal mouse calvarium, and our use of atomic force microscopy (AFM)‐based nanoindentation offered us the first opportunity to compare these small transplants against equally minute mouse bones. Our results provide insights into the long‐term behavior of newly engineered orthotopic bone from human cells and have powerful implications for therapeutic human BMSC transplantation.
ISSN:1066-5099
1549-4918
DOI:10.1634/stemcells.2005-0567