Abstract

Introduction

COPD is a disease influenced by the environment and the epigenetic modifications it generates. It could be the result of a profound epithelial dysfunction, probably at the level of Club cell subtypes, in response to a toxic environment.

Objectives

We aim to repair a pathological COPD epithelium by using induced pluripotent stem cells (iPSC) from the same patient to allow regenerating bronchial epithelia. Our hypothesis is that the re-differentiated iPSC of the patient will repair the induced damages of the cultured epithelia.

Methods

Epithelial cells were obtained from bronchial biopsies from healthy and COPD subjects and were cultured in air-liquid interface. The native bronchial epithelia have been damage mechanically. Epithelial cells derived from iPSC generated from blood of the same patients (as previously describes E. Ahmed et al., Stem Cell Res 2021) were added to the native damaged epithelium. A cell line of iPSC expressing GFP was generated. The best time and the quantity of epithelial cells derived iPSC to be added to the bronchial epithelium were explored.

Results

Cells from iPSC at the vAFE maturation level, added to the bronchial epithelium are able to adhere to the surface. A quantity of cells from iPSC approximately 30% greater than the rate of cells removed during epithelial injury was added to the bronchial epithelium. Seeding cells from iPSC directly after bronchial epithelium injury has been shown to be the most appropriate for simulating a cell therapy protocol.

Conclusions

Repairing the pathological epithelium of a patient with COPD with epithelia derived from iPSC from the same patient would make it possible to explore the avenues of a possible therapy targeting epigenetics, and why not cell therapy.