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Open Access Research article

The effect of bone allografts combined with bone marrow stromal cells on the healing of segmental bone defects in a sheep model

Marco Bernardo C Fernandes12, João Antônio Matheus Guimarães1, Priscila Ladeira Casado1, Amanda dos Santos Cavalcanti1, Natalia N Gonçalves34, Carlos E Ambrósio3*, Fernando Rodrigues4, Ana Carolina F Pinto4, Maria Angélica Miglino4 and Maria Eugênia L Duarte12

Author Affiliations

1 Basic and Clinical Research Division, National Institute of Traumatology and Orthopedics, Rio de Janeiro, Brazil

2 Institute of Biomedical Sciences, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil

3 Department of Veterinary Medicine, FZEA, USP. Faculdade de Zootecnia e Engenharia de Alimentos, Departamento de Medicina Veterinária, Universidade de São Paulo, Av. Duque de Caxias Norte, 225, 13635-900 Pirassununga, São Paulo, Brazil

4 Department of Surgery, College of Veterinary Medicine and Animal Science, University of São Paulo, São Paulo, Brazil

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BMC Veterinary Research 2014, 10:36  doi:10.1186/1746-6148-10-36

Published: 5 February 2014

Abstract

Background

The repair of large bone defects is a major orthopedic challenge because autologous bone grafts are not available in large amounts and because harvesting is often associated with donor-site morbidity. Considering that bone marrow stromal cells (BMSC) are responsible for the maintenance of bone turnover throughout life, we investigated bone repair at a site of a critically sized segmental defect in sheep tibia treated with BMSCs loaded onto allografts. The defect was created in the mid-portion of the tibial diaphysis of eight adult sheep, and the sheep were treated with ex-vivo expanded autologous BMSCs isolated from marrow aspirates and loaded onto cortical allografts (n = 4). The treated sheep were compared with control sheep that had been treated with cell-free allografts (n = 4) obtained from donors of the same breed as the receptor sheep.

Results

The healing response was monitored by radiographs monthly and by computed tomography and histology at six, ten, fourteen, and eighteen weeks after surgery. For the cell-loaded allografts, union was established more rapidly at the interface between the host bone and the allograft, and the healing process was more conspicuous. Remodeling of the allograft was complete at 18 weeks in the cell-treated animals. Histologically, the marrow cavity was reestablished, with intertrabecular spaces being filled with adipose marrow and with evidence of focal hematopoiesis.

Conclusions

Allografts cellularized with AOCs (allografts of osteoprogenitor cells) can generate great clinical outcomes to noncellularized allografts to consolidate, reshape, structurally and morphologically reconstruct bone and bone marrow in a relatively short period of time. These features make this strategy very attractive for clinical use in orthopedic bioengineering.

Keywords:
Allografts; Segmental bone defect; Bone marrow stromal cell; Animal model