Preface

The last decade has witnessed significant progress in understanding the organization and regulation of regenerative cells in the adult lung. The development and refinement of multiparameter flow cytometric cell sorting protocols and in vitro clonogenic assays has enabled the identification, prospective isolation, and characterization of candidate adult lung stem and progenitor cells. Powerful gene labelling technologies, cell lineage tracing and cell fate mapping protocols, and genetically engineered mouse models have revealed critical regulatory molecules, mechanisms, pathways, and cellular interactions important in building the lung during fetal development; and in maintaining lung function and rebuilding the lung in adulthood. This in turn has advanced the understanding of the pathophysiology of lung diseases; and how endogenous lung stem and progenitor cells, exogenous stem cells, and bioengineering technologies might be harnessed to attenuate or reverse intractable, life-threatening respiratory diseases. This is the more remarkable considering that until relatively recently the lung was generally considered a conditionally renewing organ with limited growth potential and regenerative capacity in adult life [1, 2]. Why this paradigm remained so entrenched for so long is puzzling given compelling lung cell kinetic analysis that showed that lung epithelium was continuously replaced, albeit at a very slow rate overall, that could only be explained by continuous renewal [3, 4] of postulated subsets of cells with much higher rates of turnover than the average for the organ [5]. This failure to fully appreciate that the extremely slow turnover of cells in the adult lung was not inconsistent with the existence of continuously renewing endogenous lung stem and progenitor cells able to replace senescent cells in the steady state, and regenerate functional lung cell lineages lifelong following insult or injury “blinded” the field to the potential of stem cells as therapeutic targets for adult lung regeneration and repair. Rather, research predominantly focused on understanding the pathophysiology of intractable lung diseases, and on the development of essentially palliative pharmacologic interventions to resolve inflammation and attenuate fibrotic responses induced by infectious agents, toxicants, or injury. This bias is patently obvious on interrogation of the Pubmed database as of May