OR03

Primary Ciliary Dyskinesia (PCD) is a genetic disease that alter ciliary beating, including in the respiratory airways. We hypothesized that we could restore bronchial ciliary beating with genetically corrected iPSC differentiated into air-liquid interface bronchial epithelium model (iALI) for autologous cell therapy. Different issues have to be considered: the characterization of competent cells for bronchial engraftment, the study of different strategy for previous erosion of the epithelium and the assessment of the ciliary beating recovery to assure functional repair. We use a GFP-iPSC cell line to engraft on the corresponding control cell line and mutated cell line differentiated in iALI to answer these issues. Our results suggest that lung progenitors of the embryonic stage could be the most efficient cells for engraftment. Their self-renewal ability and their capacity to differentiate in the different cell type spectrum of the bronchial epithelium are promising for the development of a long term and efficient therapy. Concerning the bronchial erosion, we considered it necessary to promote cell engraftment because of the barrier function of the intact bronchial epithelium and the lack of selection advantage from the corrected cells. Different strategies, chemical or enzymatic, seem to provide good results. Finally, several experimental conditions allowed to observe GFP engrafted cells expressing cilia, suggesting that the grafted progenitors differentiated in ciliated cells. Functional recovery still needs to be confirmed. Next step of the project is to develop the therapy for in-vivo application, assessing the safety and efficiency of the graft in immunodeficient mini-pig model.