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Researchers Develop First Mouse Model of Lung Transplantation

inflammation, which eventually lead to chronic rejection. They note that mainstay immunosuppressive drugs simply are not effective at preventing chronic rejection for lung transplants, and they hope the mouse model will reveal why.

The current hypothesis is that lung transplant rejection is linked to chronic inflammation from transient viral or bacterial infections, and this can be aggravated by the fact that transplant recipients are taking immunosuppressive drugs, Kreisel said.

Mouse models for heart, liver and kidney transplants have existed for years, but developing a similar model for lung transplantation has proved to be a real technical challenge. Mouse lungs measure less than an inch in length and the pulmonary vein and artery, which carry blood to and from the heart, are as thin as human hair.

Mikio Okazaki, M.D., a postdoctoral fellow, adapted the lung transplantation technique used in rats to the mice. He uses synthetic cuffs to join the donor vessels with those of the recipient. Okazaki has successfully performed several hundred lung transplants in the mice, and the teams analysis indicates the model simulates the same immune response that occurs in humans following lung transplantation.

Before Okazaki and his Washington University colleagues developed the mouse model, researchers had been studying lung transplantation using a nonphysiological mouse model in which a small section of trachea from one mouse was transplanted under the skin of another. Although it was simple to create, the model did not accurately mimic lung transplantation.

It was a very artificial model that had little to do with reality. We think the new model will be far better for studying the underlying immune mechanisms that lead to rejection, Okazaki said.

The new mouse lung transplant model has an advantage over those in rats and larger animals because the genetics of mice are well documented a
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