Benefits of bronchial epithelial repair by iPSCs in COPD

COPD is a disease influenced by environmental factors and the resulting epigenetic modifications. The underlying cause may involve significant dysfunction in epithelial repair. Our aim is to improve airway epithelial repair in COPD by transplanting pre-differentiated induced pluripotent stem cells (iPSC) from the same patient. Epithelial cells from bronchial biopsies were cultured in ALI (air-liquid interface). Native bronchial epithelia were mechanically damaged. iPSC-derived epithelial cells from patient blood (E. Ahmed et al., Stem Cell Res, 2021) were engineered to express or not GFP. Reprogrammed iPSC were differentiated to the early vAFE (ventral foregut endodermis) stage and added to damaged native epithelium. GFP expression was monitored by fluorescence microscopy from the day of transplantation and for 42 days to monitor lesion repair and to assess differentiation of transplanted cells. The formalin-fixed culture wells were then subjected to immunofluorescence labelling (GFP, eCAD, p63). GFP cells derived from vAFE-stage iPSC were successfully transplanted to the site of the ALI epithelial lesion. This was confirmed by observation of GFP under a fluorescence microscope. The detection of fluorescence on day 3, which intensified until day 7, was still present on day 42, underlining the long-lasting viability and stability of the transplanted cultures. Immunofluorescence staining at day 7 also demonstrated that GFP+ cells formed intercellular junctions (eCAD) with GFP- cells. Some GFP+ cells were also found to be p63+. It's possible to repair the pathological epithelium of a COPD patient using iPSC-derived epithelium. The repair mechanisms could provide clues to therapeutic avenues, targeting epigenetics and cell therapy?