Differentiation of Human Induced Pluripotent Stem Cells from Patients with Severe COPD into Functional Airway Epithelium

Engi Ahmed (1, 2, 3) , Mathieu Fieldes (1, 2) , Chloé Bourguignon (1, 2) , Joffrey Mianné (1, 2) , Aurélie Petit (3, 4) , Myriam Jory (5) , Chantal Cazevieille (6) , Hassan Boukhaddaoui (6) , James Garnett (7, 8) , Christophe Hirtz (1, 2) , Gladys Massiera (5) , Isabelle Vachier (3, 4) , Said Assou (1, 2) , Arnaud Bourdin (9, 10, 3) , John de Vos (1, 2, 11)

1 Cellules Souches, Plasticité Cellulaire, Médecine Régénératrice et Immunothérapies (IRMB)
2 CHU Montpellier
3 Hôpital Arnaud de Villeneuve [CHRU Montpellier]
4 UM - Université de Montpellier
5 L2C - Laboratoire Charles Coulomb
6 INM - Institut des Neurosciences de Montpellier
7 Boehringer Ingelheim Pharma GmbH & Co. KG
8 Newcastle University [Newcastle]
9 PhyMedExp - Physiologie & médecine expérimentale du Cœur et des Muscles [U 1046]
10 CHRU Montpellier - Centre Hospitalier Régional Universitaire [Montpellier]
11 CHRU Montpellier - Hôpital Saint Eloi

Background: Chronic Obstructive Pulmonary Disease (COPD), a major cause of mortality and disability, is a complex disease with heterogeneous and ill-understood biological mechanisms. Human induced pluripotent stem cells (hiPSCs) are a promising tool to model human disease, including the impact of genetic susceptibility. Methods: We developed a simple and reliable method for reprogramming peripheral blood mononuclear cells into hiPSCs and to differentiate them into air–liquid interface bronchial epithelium within 45 days. Importantly, this method does not involve any cell sorting step. We reprogrammed blood cells from one healthy control and three patients with very severe COPD. Results: The mean cell purity at the definitive endoderm and ventral anterior foregut endoderm (vAFE) stages was >80%, assessed by quantifying C-X-C Motif Chemokine Receptor 4/SRY-Box Transcription Factor 17 (CXCR4/SOX17) and NK2 Homeobox 1 (NKX2.1) expression, respectively. vAFE cells from all four hiPSC lines differentiated into bronchial epithelium in air–liquid interface conditions, with large zones covered by beating ciliated, basal, goblets, club cells and neuroendocrine cells, as found in vivo. The hiPSC-derived airway epithelium (iALI) from patients with very severe COPD and from the healthy control were undistinguishable. Conclusions: iALI bronchial epithelium is ready for better understanding lung disease pathogenesis and accelerating drug discovery.

Keywords: airway epithelium; chronic obstructive pulmonary disease; disease modeling; human induced pluripotent stem cells

Domains: Life Sciences [q-bio]

Engi Ahmed, Mathieu Fieldes, Chloé Bourguignon, Joffrey Mianné, Aurélie Petit, et al.. Differentiation of Human Induced Pluripotent Stem Cells from Patients with Severe COPD into Functional Airway Epithelium. Cells, 2022, 11 (15), pp.2422. ⟨10.3390/cells11152422⟩. ⟨hal-03751524⟩