Development of a Cyclosporin-A-Induced Immune Tolerant Rat Model to Test Marrow Allograft Cell Type Effects on Bone Repair
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Bone repair is an important concept in tissue engineering, and the ability to repair bone in hypotrophic conditions such as that of irradiated bone, represents a challenge for this field. Previous studies have shown that a combination of bone marrow and (BCP) was effective to repair irradiated bone. However, the origin and role played by each cell type in bone healing still remains unclear. In order to track the grafted cells, the development of an animal model that is immunotolerant to an allograft of bone marrow would be useful. Furthermore, because the immune system interacts with bone turnover, it is of critical importance to demonstrate that immunosuppressive drugs do not interfere with bone repair. After a preliminary study of immunotolerance, cyclosporin-A was chosen to be used in immunosuppressive therapy. Ten rats were included to observe qualitative and quantitative bone repair 8 days and 6 weeks after the creation of bone defects. The defects were filled with an allograft of bone marrow alone or in association with BCP under immunosuppressive treatment (cyclosporin-A). The results showed that there was no significant interaction of cyclosporin-A with osseous regeneration. The use of this new immunotolerant rat model of bone marrow allograft in future studies will provide insight on how the cells within the bone marrow graft contribute to bone healing, especially in irradiated conditions.
KeywordsBone repair Bone marrow allograft Cyclosporin-A Immunotolerance Cell tracking
This work was supported by Grants from ‘‘les gueules cassées’’ foundation and Sanofi Aventis Laboratories (perspectives ORL 2009). We thank Biomatlante (Vigneux de Bretagne, France) for supplying materials. We thank Dr Françoise Accard and Dr Antoine Rouger for their contribution to this work.
Conflict of Interest
The authors declare no conflict of interest.
Human and Animal Rights and Informed Consent
All the animals were provided by a certified breeding center (R. Janvier, Le Genest St. Isle, France). Animal care was provided by the Experimental Therapeutic Unit (Faculty of Medicine of Nantes, France), in accordance with the institutional guidelines of the French Ethical Committee (CEEA.PdL.06) for conducting animal experiments. The European Community Guidelines for the Care and Use of Laboratory Animals (DE 86/609/CEE, modified DE 2003/65/CE) have been revised by the European Directive 2010 (DE 2010/63/UE modified 22/09/2010). The adoption of the UE regulations into the French guidelines is effective as of January 1, 2013. Submission of the project to the new Ethical Committee of the “Pays de la Loire” was not mandatory until January 1, 2013. Nevertheless, all of the experiments conducted prior to January 2013 were performed according to these new regulations.
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