Hana Kotasová1,2, Michaela Capandová1, Vendula Pelková1, Jana Dumková1, Zuzana Koledová1, Ján Remšík2,3,4,5, Karel Souček2,3,4, Zuzana Garlíková1, Veronika Sedláková1, Anas Rabata1, Petr Vaňhara1,2, Lukáš Moráň1,6, Lukáš Pečinka2,7, Volodymyr Porokh1, Martin Kučírek1, Libor Streit8,9, Josef Havel2,7, Aleš Hampl10,11. 1. Department of Histology and Embryology, Faculty of Medicine, Masaryk University, Kamenice 753/5, 625 00, Brno, Czech Republic. 2. International Clinical Research Center, St. Anne's University Hospital, Brno, Czech Republic. 3. Institute of Biophysics, The Czech Academy of Sciences, Brno, Czech Republic. 4. Department of Experimental Biology, Faculty of Science, Masaryk University, Brno, Czech Republic. 5. Current Address: Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York City, NY, USA. 6. Research Centre for Applied Molecular Oncology (RECAMO), Masaryk Memorial Cancer Institute, Brno, Czech Republic. 7. Department of Chemistry, Faculty of Science, Masaryk University, Brno, Czech Republic. 8. Department of Plastic and Cosmetic Surgery, Faculty of Medicine, Masaryk University, Brno, Czech Republic. 9. Department of Plastic and Cosmetic Surgery, St. Anne's Faculty Hospital, Brno, Czech Republic. 10. Department of Histology and Embryology, Faculty of Medicine, Masaryk University, Kamenice 753/5, 625 00, Brno, Czech Republic. ahampl@med.muni.cz. 11. International Clinical Research Center, St. Anne's University Hospital, Brno, Czech Republic. ahampl@med.muni.cz.
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.
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.
Authors: Alyssa J Miller; David R Hill; Melinda S Nagy; Yoshiro Aoki; Briana R Dye; Alana M Chin; Sha Huang; Felix Zhu; Eric S White; Vibha Lama; Jason R Spence Journal: Stem Cell Reports Date: 2017-12-14 Impact factor: 7.765
Authors: Ya-Wen Chen; Sarah Xuelian Huang; Ana Luisa Rodrigues Toste de Carvalho; Siu-Hong Ho; Mohammad Naimul Islam; Stefano Volpi; Luigi D Notarangelo; Michael Ciancanelli; Jean-Laurent Casanova; Jahar Bhattacharya; Alice F Liang; Laura M Palermo; Matteo Porotto; Anne Moscona; Hans-Willem Snoeck Journal: Nat Cell Biol Date: 2017-04-24 Impact factor: 28.824
Authors: William J Zacharias; David B Frank; Jarod A Zepp; Michael P Morley; Farrah A Alkhaleel; Jun Kong; Su Zhou; Edward Cantu; Edward E Morrisey Journal: Nature Date: 2018-02-28 Impact factor: 49.962