J Korean Assoc Oral Maxillofac Surg.  2010 Oct;36(5):353-359.

The immunosuppression effect of cyclosporine A on the allogenic calvarial bone graft in mice

• Kim BS
• Park SM
• Kim KR
• Jeoung Y
• Han MS
• Kook MS
• Park HJ
• Ryu SY
• Oh HK

Abstract

INTRODUCTION
This study examined the effect of cyclosporine A (CsA) on the allogenic cranial bone graft in the mice.
MATERIALS AND METHODS
Twenty eight 12-week-old male ICR mice weighing 40 g were used. The experimental group was injected subcutaneously with CsA (10 mg/kg/day) diluted in Caster oil for 7 days prior to the graft until sacrifice. The control group was injected with the same solution without CsA.
RESULTS
In the experimental group, fibrous connective tissues and small amounts of inflammatory cells were observed. At 2 weeks after the allograft in the experimental group, new bone formation in fibrous collagenous tissue and around the allogenic bone was noted. At 4 weeks after the allograft, new bone formation was active along and at the periphery of the mature allogenic bone. The proliferation of blood vessels increased in bone marrow. In the control group, fibrous tissues and inflammatory cells were observed around the allogenic bone and existing bone at 1 week. At 2 weeks after the allograft, the proliferation of blood vessels accompanied by inflammatory cells were scattered in the fibrous connective tissues. New bone formation around the allogenic and existing bone could be observed. At 4 weeks after the allograft, inflammatory cells were severely infiltrated around the allogenic bone. Osteoclasts were scattered along the allogenic bone and induced bone resorption.
CONCLUSION
These results suggest that the daily administration of CsA (10 mg/kg/day) induces efficient immunosuppression without serious complications ,and this protocol might be useful for the experimental model of allogenic bone grafts.

Keyword

Cyclosporine A; Allogenic bone graft; Allograft; Immunosuppression; Osteoclasts

MeSH Terms

Animals
Blood Vessels
Bone Marrow
Collagen
Connective Tissue
Cyclosporine
Humans
Immunosuppression
Male
Mice
Mice, Inbred ICR
Models, Theoretical
Osteoclasts
Osteogenesis
Transplantation, Homologous
Transplants
Collagen
Cyclosporine

Figure

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  Fig. 1. Intraoperative photograph. Bone defects in both parietal bones and two 3 mm-sized calvarial bone discs derived from the same mouse were shown.

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  Fig. 2. Photomicrograph of 1 week after allograft in the control group. Fibrous tissues and inflammatory cells are observed around allogenic bone and host bone. Some osteocytes in the lacunae and the necrosis of bone marrow can be seen in grafted bone.(H&E staining, original magnification ×100, × 200)

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  Fig. 3. Photomicrograph of 2 weeks after allograft in the control group. The proliferation of blood vessels in bone marrow is increased. Some osteocytes the necrosis of bone marrow of grafted bone are observed. Osteocytes newly formed marrow are observed in woven bone.(H&E staining, original magnification ×100, ×200)

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  Fig. 4. Photomicrograph of 4 weeks after allograft in the control group. Infiltration of severe inflammatory cells around the allogenic bone is noted. Osteoclasts along the allogenic bone with bone resorption are observed. And some osteocytes in the lacunae of grated bone are still alive.(H&E staining, original magnification ×100, ×200)

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  Fig. 5. Photomicrograph of normal thymus. The thymus comprises a densely staining peripheral region (cortex) and a lighter staining central portion (medulla).(H&E staining, original magnification ×40)

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  Fig. 6. Photomicrograph of 1 week after allograft in the experimental group. Fibrous connective tissues and small amounts of inflammatory cells are shown. Many osteocytes in the lacunae of grated bone are alive and the necrosis of bone marrow of grafted bone is noted.(H&E staining, original magnification ×40, ×100)

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  Fig. 7. Photomicrograph of 2 weeks after allograft in the experimental group. Newly formed marrow in woven bone is noted. Many osteocytes in the lacunae of grated bone and the necrosis of bone marrow of grafted bone can be observed.(H&E staining, original magnification ×100, ×100, ×200)

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  Fig. 8. Photomicrograph of 4 weeks after allograft in the experimental group. The proliferation of blood vessels in bone marrow is seen. The maturation of newly formed marrow in woven bone and the necrosis of bone marrow of grafted bone is observed. Some osteocytes are still seen in the lacunae of grated bone.(H&E staining, original magnification ×40, ×100)

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  Fig. 9. Photomicrograph of thymus at 2 weeks and 4 weeks after cyclosporine injection. The whole thymus is destructed and has not germinal center.(H&E staining, original magnification ×40)

Reference

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