Tissue Eng Regen Med.  2022 Oct;19(5):1033-1050. 10.1007/s13770-022-00458-0.

Expandable Lung Epithelium Differentiated from Human Embryonic Stem Cells

Affiliations
  • 1Department of Histology and Embryology, Faculty of Medicine, Masaryk University, Kamenice 753/5, 625 00 Brno, Czech Republic
  • 2International Clinical Research Center, St. Anne’s University Hospital, Brno, Czech Republic
  • 3Institute of Biophysics, The Czech Academy of Sciences, Brno, Czech Republic
  • 4Research Centre for Applied Molecular Oncology (RECAMO), Masaryk Memorial Cancer Institute, Brno, Czech Republic
  • 5Department of Chemistry, Faculty of Science, Masaryk University, Brno, Czech Republic
  • 6Department of Experimental Biology, Faculty of Science, Masaryk University, Brno, Czech Republic
  • 7Current Address: Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York City, NY, USA
  • 8Department of Plastic and Cosmetic Surgery, Faculty of Medicine, Masaryk University, Brno, Czech Republic
  • 9Department of Plastic and Cosmetic Surgery, St. Anne’s Faculty Hospital, Brno, Czech Republic

Abstract

BACKGROUND
The progenitors to lung airway epithelium that are capable of long-term propagation may represent an attractive source of cells for cell-based therapies, disease modeling, toxicity testing, and others. Principally, there are two main options for obtaining lung epithelial progenitors: (i) direct isolation of endogenous progenitors from human lungs and (ii) in vitro differentiation from some other cell type. The prime candidates for the second approach are pluripotent stem cells, which may provide autologous and/or allogeneic cell resource in clinically relevant quality and quantity.
METHODS
By exploiting the differentiation potential of human embryonic stem cells (hESC), here we derived expandable lung epithelium (ELEP) and established culture conditions for their long-term propagation (more than 6 months) in a monolayer culture without a need of 3D culture conditions and/or cell sorting steps, which minimizes potential variability of the outcome.
RESULTS
These hESC-derived ELEP express NK2 Homeobox 1 (NKX2.1), a marker of early lung epithelial lineage, display properties of cells in early stages of surfactant production and are able to differentiate to cells exhibitting molecular and morphological characteristics of both respiratory epithelium of airway and alveolar regions.
CONCLUSION
Expandable lung epithelium thus offer a stable, convenient, easily scalable and high-yielding cell source for applications in biomedicine.

Keyword

Lung; Epithelium; hESC; Differentiation; Foregut endoderm
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