Bone marrow-derived mesenchymal cells can rescue osteogenic capacity of devitalized autologous bone.
In clinical cases, many orthopaedists have been troubled with bone fragility, such as fractures after devitalization therapy for bone tumour, pathological fractures and metastatic tumours. The aim of this study was to determine whether loss of osteogenic capacity of devitalized autologous bones can be rescued using cultured bone marrow-derived mesenchymal cells. A devitalized bone model was produced from rat femur by irradiation and three groups were prepared: intact bone, irradiated bone and irradiated bone combined with cultured mesenchymal cells. Each bone was transplanted subcutaneously into a syngeneic rat. At 2 or 4 weeks after transplantation, biochemical analyses [alkaline phosphatase (ALP) activity and osteocalcin mRNA expression] and histological measurement were performed. Moreover, we verified the origin of newly formed bone, using the sex-determining region Y (sry) gene as a marker to distinguish between donor and recipient. In both intact bone and irradiated bone with mesenchymal cells, ALP activity and osteocalcin mRNA expression were detected and living osteoblasts together with newly formed bone were clearly seen histologically. Furthermore, analysis of the origin of de novo formed bone indicated that newly formed bone in irradiated bone with mesenchymal cells was derived from cultured bone marrow-derived mesenchymal cells. These results proved that the osteogenic capacity of devitalized autologous bone can be rescued using tissue-engineering techniques. This procedure should contribute to various clinical treatments, such as local metastatic tumours, pathological fracture after devitalization therapy and reconstruction after wide-margin tumour resection. The benefits would be applicable to all types of devitalized bone.
Tohma
Yasuaki
Y
Department of Orthopaedic Surgery, Nara Medical University, Kashihara, Japan. SNC45147@nifty.com
Ohgushi
Hajime
H
Morishita
Toru
T
Dohi
Yoshiko
Y
Tadokoro
Mika
M
Tanaka
Yasuhito
Y
Takakura
Yoshinori
Y
D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D015415:Biomarkers; D001854:Bone Marrow Cells / Q000166:cytology* / Q000378:metabolism; D016025:Bone Transplantation; D001842:Bone and Bones / Q000166:cytology* / Q000378:metabolism / Q000601:surgery; D002478:Cells, Cultured; D005260:Female; D005786:Gene Expression Regulation; D008297:Male; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000378:metabolism; D015675:Osteocalcin / Q000235:genetics; D010012:Osteogenesis; D051381:Rats; D011916:Rats, Inbred F344; D014182:Transplantation, Autologous; D014998:Y Chromosome / Q000235:genetics
D015415:Biomarkers; D015675:Osteocalcin; D000469:Alkaline Phosphatase