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Cell Delivery in Pigs/Mice

Lung disease is the leading cause for morbidity and mortality in the US and worldwide. Although lung transplantation might be the only option for severe pulmonary diseases, cellular therapy has offered an alternative approach for treating various less severe lung diseases. We are mostly interested in developing a stem cell-based therapy for treating cystic fibrosis (CF) lung disease. Rodent models including mice and rats were used to develop and evaluate the efficiency of a novel intratracheal method for instillation of lung epithelial cells in vivo. To preclinically evaluate this novel treatment for lung diseases, we also delivered exogenous cells into the lungs of pigs and have observed robust cell engraftment. Our studies provided important background for future preclinical evaluation of intratracheal cell transplantation to treat lung diseases. Currently we are generating lung epithelial cells from iPSCs and will be looking at the restoration of lung functions in CF pigs following intratracheal delivery of these iPSC-derived pulmonary cells.

Retention of cells in pig lungs: 100 x 106 GFP-labeled A549 cells were delivered to one lobe of the pig lung and the cell retention was determined after 24 h. A-C, Lung sections from control pigs; D-F, Lung sections from animals received cell delivery. Lung sections were immunostained with anti-GFP followed by Alexa Fluor 555-conjugated IgG (Red) (A and D) and counterstained with DAPI (B and E), or stained for H&E (C and F).