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Method Article

Heterotopic and Orthotopic Tracheal Transplantation in Mice used as Models to Study the Development of Obliterative Airway Disease

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DOI:

10.3791/1437

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January 20th, 2010

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In This Article

Summary

This video shows and compares two experimental models to study the development of obliterative airway disease (OAD) in mice, the heterotopic and orthotopic tracheal transplantation model.

Abstract

Obliterative airway disease (OAD) is the major complication after lung transplantations that limits long term survival (1-7).

To study the pathophysiology, treatment and prevention of OAD, different animal models of tracheal transplantation in rodents have been developed (1-7). Here, we use two established models of trachea transplantation, the heterotopic and orthotopic model and demonstrate their advantages and limitations.

For the heterotopic model, the donor trachea is wrapped into the greater omentum of the recipient, whereas the donor trachea is anastomosed by end-to-end anastomosis in the orthotopic model.

In both models, the development of obliterative lesions histological similar to clinical OAD has been demonstrated (1-7).

This video shows how to perform both, the heterotopic as well as the orthotopic tracheal transplantation technique in mice, and compares the time course of OAD development in both models using histology.

Protocol

  1. Male Balb/C mice (8-12 weeks) are purchased from Charles River Laboratories (Sulzfeld, Germany). The mice are housed under conventional conditions, fed standard mice food and water ad libitum.
  2. 2% Isofluran is used for anesthesia.

DONOR PREPARATION

  1. Shave the abdominal hair and disinfect the area using betaisodona.
  2. Under microscopic view, perform a midline cervical incision from the level of the larynx to the sternum.
  3. Remove the subcutaneous fat and the strap muscles to get a clear view of the trachea.
  4. Dissect the trachea from any surrounding tissues, like the esophagus, nerves, arte....

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Discussion

Mice are available in different transgeneic and knockout model, and therefore suitable to study mechanistic questions related to OAD (4).
Both models of tracheal transplantation shown in this video can be used as reliable models for studying OAD development.
However, each model demonstrates advantages and limitations.

The heterotopic tracheal transplantation is easy to perform and does not require special surgical training (3, 5). After het.......

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Disclosures

Sonja Schrepfer has received a research grant from the Deutsche Forschungsgemeinschaft (DFG) (SCHR992/3–1).]

All animals received human care in compliance with the Principles of Laboratory Animal Care, experiments on animals were performed in accordance with the guidelines and regulations set forth by the National Society for Medical research and the Guide for the Care and Use of Laboratory Animals published by the National Institutes of Health (National Institutes of Health publication 85-23, revised 1985).

All animals were obtained from Charles River Laboratories (Sulzfeld, Germany) and were maintained in the animal care facilities of the University Hospital Hamburg Eppendorf. The animals received standard chow and water ad libitum.

Acknowledgements

The authors thank Christiane Pahrmann (Lab Manager).

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References

  1. Adams, B., Berry, G., Huang, X., Shorthouse, R., Brazelton, T., Morris, R. Immunosuppressive therapies for the prevention and treatment of obliterative airway disease in heterotopic rat trachea allografts. Transplantation. 69, 2260-2266 Forthcoming.
  2. Adams, B., Brazelton, T., Berry, G., Morris, R.

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