The use of pre-conditioning and novel assays in the development of protocols for transplantation of lung progenitors

The World Health Organization ranks lung diseases among the leading causes of morbidity and mortality worldwide. The definitive treatment for rapidly progressing and end-stage respiratory disease is lung transplantation, but due to the shortage of suitable donor lungs, this treatment is available only to a limited number of patients suffering from terminal lung disease. Advances in our understanding of lung biology suggest that this challenge could potentially be addressed by stem cell-based therapies. To this end, it is crucial to develop strategies for the use of allogeneic donors, as well as reliable animal assays for investigation of different lung progenitors, allowing us to determine their short- and long-term differentiation potential along different lung cell lineages, their self-renewal and the optimal administration route, as well as their morphological and functional curative capabilities in various disease models. In this chapter, we review a novel approach for attaining this goal, based on insights gained over a number of years from HSC transplantation, with special emphasis on the role of adequate pre-conditioning.