Benefits of bronchial epithelial repair by iPSCs in COPD

COPD is a disease influenced by the environment and the epigenetic modifications it causes. This pathology could be the result of a profound dysfunction of epithelial repair. We aim to improve the repair of COPD airway epithelium by grafting pre-differentiated induced pluripotent stem cells (iPSCs) from the same patient. Epithelial cells were obtained from bronchial biopsies and were cultured in air-liquid interface (ALI). Pseudostratified native bronchial epithelia were mechanically damaged under different conditions. iPSC-derived epithelial cells were generated from the blood of the same patients (E. Ahmed et al., Stem Cell Res, 2021) and modified to express or not express GFP. Cells from reprogrammed IPS were differentiated to the early maturation stage vAFE (ventral Anterior Foregut Endoderm) and were added to the lesion level of native damaged epithelia. GFP expression was observed by fluorescence optical microscopy from the day of transplantation and for 7 days to follow repair of the lesion. The culture wells were then fixed with formaldehyde to carry out immunofluorescence markings (GFP, EpCAM). GFP cells derived from iPSCs at the vAFE stage were successfully grafted to the injury site of the ALI epithelium. This was confirmed by the presence of GFP under the optical fluorescence microscope with detection of fluorescence on D3 which increased until D7. The immunofluorescence markings after fixation on day 7 of the cells show that the GFP+ cells are also EpCAM+. Repairing the pathological epithelium of a COPD patient with epithelia derived from iPSCs is possible. The mechanisms repair need to be explored and would make it possible to study avenues for a possible therapy targeting epigenetics, and why not cell therapy.