Lung injuries that impact the alveolus, such as emphysema, pulmonary fibrosis, and acute lung injury, are costly and prevalent problems. Moreover, the extent of alveolar injury and impairment of gas exchange is strongly associated with prognosis and survival. Thus, mechanisms of repair and regeneration of the lung alveolar compartment have received mounting attention as newer approaches to the study of stem and progenitor cells in this region unfold. The role of type II alveolar epithelial as the sole source of type I (AECI) and II (AECII) alveolar epithelial cells following lung injury has been recently challenged; recently, investigators have described stemprogenitor cells that function like precursors to AECII either in vitro or in vivo, both in mice and humans. Techniques to explore selfrenewal and multipotency have been rigorously applied to these putative stem-progenitor cell populations and the data thus far is compelling. This review provides background to the study of alveolar regeneration with the aim to provide context to the recent discoveries of putative stem-progenitor cells that may contribute to this process.
Emphysema is a progressive, disabling pulmonary disease characterized by destruction of elastic lung tissue. It results in hyperinflation, and loss of recoil, and medical therapies are of limited benefit. Lung volume reduction surgery (LVRS) has recently emerged as an effective therapy for emphysema. LVRS involves surgical resection of diseased lung, allowing more space within the chest cavity for the remaining lung to expand and function. Unfortunately, LVRS is associated with substantial mortality (5–10%), morbidity (20–40%) and cost ($25–35,000 per operation). We have recently developed a safer, effective, and less costly approach to lung volume reduction therapy based on tissue engineering principles that can be administered through a bronchoscope. Testing of this procedure required the development of a large animal model that accurately reproduces the physiology of emphysema. This report summarizes the development and validation of such a model, and the testing of our approach, known as Bronchoscopic Lung Volume Reduction (BLVR). The model has facilitated refinement of the procedure in preparation for clinical trials.
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