Pascal Duchesneau

For end-stage lung disease, lung transplantation remains the only treatment but is limited by the availability of organs. Production of bioengineered lungs via recellularization is an alternative but is hindered by inadequate repopulation. We present a cell delivery method via the generation of negative pressure. Decellularized lungs were seeded with human bronchial epithelial cells using gravity-based perfusion or negative pressure (via air removal). After delivery, lungs were maintained in static conditions for 18 hrs, and cell surface coverage was qualitatively assessed using histology and analyzed by subjective scoring and an image analysis software. Negative pressure seeded lungs had higher cell surface coverage area, and this effect was maintained following five days of culture. Enhanced coverage via negative pressure cell delivery was also observed when vasculature seeded with endothelial cells. Our findings show that negative pressure cell delivery is a superior approach for the recellularization of the bioengineered lung.

Cystic Fibrosis (CF) is a chronic autosomal recessive disease caused by defects in the cystic fibrosis transmembrane conductance regulator gene (CFTR). Cystic Fibrosis affects multiple organs but progressive remodeling of the airways, mucus accumulation, and chronic inflammation in the lung, result in lung disease as the major cause of morbidity and mortality. While advances in management of CF symptoms have increased the life expectancy of this devastating disease, and there is tremendous excitement about the potential of new agents targeting the CFTR molecule itself, there is still no curative treatment. With the recent advances in the identification of endogenous airway progenitor cells and in directed differentiation of pluripotent cell sources, cell-based therapeutic approaches for CF have become a plausible treatment method with the potential to ultimately cure the disease. In this review, we highlight the current state of cell therapy in the CF field focusing on the relevant autologous and allogeneic cell populations under investigation and the challenges associated with their use. In addition, we present advances in induced pluripotent stem (iPS) cell approaches and emerging new genetic engineering methods, which have the capacity to overcome the current limitations hindering cell therapy approaches.