Clinical lung transplantation has developed over the past several years into a viable therapeutic option for many types of end-stage lung disease. Most patients benefiting from this therapy are adults with various types of end-stage emphysema, primary pulmonary hypertension, restrictive lung disease such as pulmonary fibrosis, and cystic fibrosis. Relatively few children are in need of lung transplantation, and because of a lack of donor organs, fewer still actually undergo this life-saving surgery. In 1995, nearly one-third of children on the lung transplant waiting list died while waiting a suitable organ. The investigators and others have already reported on the experimental and clinical application of """"""""reduced size"""""""" lung transplantation in which part of a more mature lung is transplanted into a smaller recipient in order to identify more donor organs for the pediatric population. Previous work on this project focused on examining the long-term functional results of reduced-size transplants and whether or not they were superior to size-matched immature whole lung transplants. In addition, the authors briefly began to identify the growth potential of reduced-size lung transplants, but only at a whole-organ level. It was found that a mature lobe transplanted into an immature recipient does have the ability to grow. The stimulus for and the cellular basis of this lung growth are unknown and are the focus of continued research. Studies will continue to be done in a porcine model of lung transplantation with which we are very familiar. New studies propose to identify factors present in the immature host environment which are responsible for lung growth and differentiation and how they may stimulate further growth of an already mature lobar transplant. Pneumocyte division and differentiation potential will also be examined. The time course and molecular modulation of normal pig lung growth and development will be studied to allow further interpretation of experimental results in the transplanted lungs. In addition, the effects of chronic rejection on growth potential of transplanted lungs will also be examined at the cellular and whole organ level. Identification of molecular modulators of normal lung development and their effects on cellular events of transplanted lungs will not only advance the field of lung transplantation, but will also form a basis for potential new treatments of other types of lung injury and provide a better understanding of lung growth following lung transplantation.
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