2022
Kotasová, Hana; Capandová, Michaela; Pelková, Vendula; Dumková, Jana; Koledová, Zuzana; Remšík, Ján; Souček, Karel; Garlíková, Zuzana; Sedláková, Veronika; Rabata, Anas; Vaňhara, Petr; Moráň, Lukáš; Pečinka, Lukáš; Porokh, Volodymyr; Kučírek, Martin; Streit, Libor; Havel, Josef; Hampl, Aleš
Expandable Lung Epithelium Differentiated from Human Embryonic Stem Cells. Journal Article
In: Tissue engineering and regenerative medicine, vol. 19, no. 5, pp. 1033–1050, 2022, ISSN: 2212-5469 1738-2696, (Place: Korea (South)).
Abstract | Links | BibTeX | Tags: *Human Embryonic Stem Cells, Cell Differentiation, Differentiation, Epithelium, Foregut endoderm, hESC, Humans, Lung, Lung/metabolism, Surface-Active Agents/metabolism
@article{kotasova_expandable_2022,
title = {Expandable Lung Epithelium Differentiated from Human Embryonic Stem Cells.},
author = {Hana Kotasová and Michaela Capandová and Vendula Pelková and Jana Dumková and Zuzana Koledová and Ján Remšík and Karel Souček and Zuzana Garlíková and Veronika Sedláková and Anas Rabata and Petr Vaňhara and Lukáš Moráň and Lukáš Pečinka and Volodymyr Porokh and Martin Kučírek and Libor Streit and Josef Havel and Aleš Hampl},
doi = {10.1007/s13770-022-00458-0},
issn = {2212-5469 1738-2696},
year = {2022},
date = {2022-10-01},
journal = {Tissue engineering and regenerative medicine},
volume = {19},
number = {5},
pages = {1033–1050},
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.},
note = {Place: Korea (South)},
keywords = {*Human Embryonic Stem Cells, Cell Differentiation, Differentiation, Epithelium, Foregut endoderm, hESC, Humans, Lung, Lung/metabolism, Surface-Active Agents/metabolism},
pubstate = {published},
tppubtype = {article}
}
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.
Lenárt, Sára; Lenárt, Peter; Knopfová, Lucia; Kotasová, Hana; Pelková, Vendula; Sedláková, Veronika; Vacek, Ondřej; Pokludová, Jana; Čan, Vladimír; Šmarda, Jan; Souček, Karel; Hampl, Aleš; Beneš, Petr
TACSTD2 upregulation is an early reaction to lung infection. Journal Article
In: Scientific reports, vol. 12, no. 1, pp. 9583, 2022, ISSN: 2045-2322, (Place: England).
Abstract | Links | BibTeX | Tags: *Antigens, *Cell Adhesion Molecules/metabolism, Animals, Epithelial Cells/metabolism, Lung/metabolism, Neoplasm/metabolism, Up-Regulation
@article{lenart_tacstd2_2022,
title = {TACSTD2 upregulation is an early reaction to lung infection.},
author = {Sára Lenárt and Peter Lenárt and Lucia Knopfová and Hana Kotasová and Vendula Pelková and Veronika Sedláková and Ondřej Vacek and Jana Pokludová and Vladimír Čan and Jan Šmarda and Karel Souček and Aleš Hampl and Petr Beneš},
doi = {10.1038/s41598-022-13637-9},
issn = {2045-2322},
year = {2022},
date = {2022-06-01},
journal = {Scientific reports},
volume = {12},
number = {1},
pages = {9583},
abstract = {TACSTD2 encodes a transmembrane glycoprotein Trop2 commonly overexpressed in carcinomas. While the Trop2 protein was discovered already in 1981 and first antibody-drug conjugate targeting Trop2 were recently approved for cancer therapy, the physiological role of Trop2 is still not fully understood. In this article, we show that TACSTD2/Trop2 expression is evolutionarily conserved in lungs of various vertebrates. By analysis of publicly available transcriptomic data we demonstrate that TACSTD2 level consistently increases in lungs infected with miscellaneous, but mainly viral pathogens. Single cell and subpopulation based transcriptomic data revealed that the major source of TACSTD2 transcript are lung epithelial cells and their progenitors and that TACSTD2 is induced directly in lung epithelial cells following infection. Increase in TACSTD2 expression may represent a mechanism to maintain/restore epithelial barrier function and contribute to regeneration process in infected/damaged lungs.},
note = {Place: England},
keywords = {*Antigens, *Cell Adhesion Molecules/metabolism, Animals, Epithelial Cells/metabolism, Lung/metabolism, Neoplasm/metabolism, Up-Regulation},
pubstate = {published},
tppubtype = {article}
}
TACSTD2 encodes a transmembrane glycoprotein Trop2 commonly overexpressed in carcinomas. While the Trop2 protein was discovered already in 1981 and first antibody-drug conjugate targeting Trop2 were recently approved for cancer therapy, the physiological role of Trop2 is still not fully understood. In this article, we show that TACSTD2/Trop2 expression is evolutionarily conserved in lungs of various vertebrates. By analysis of publicly available transcriptomic data we demonstrate that TACSTD2 level consistently increases in lungs infected with miscellaneous, but mainly viral pathogens. Single cell and subpopulation based transcriptomic data revealed that the major source of TACSTD2 transcript are lung epithelial cells and their progenitors and that TACSTD2 is induced directly in lung epithelial cells following infection. Increase in TACSTD2 expression may represent a mechanism to maintain/restore epithelial barrier function and contribute to regeneration process in infected/damaged lungs.