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.
2017
Tylichová, Zuzana; Straková, Nicol; Vondráček, Jan; Vaculová, Alena Hyršlová; Kozubík, Alois; Hofmanová, Jiřina
In: The Journal of nutritional biochemistry, vol. 39, pp. 145–155, 2017, ISSN: 1873-4847 0955-2863, (Place: United States).
Abstract | Links | BibTeX | Tags: Antineoplastic Agents/pharmacology, Apoptosis/*drug effects, Autophagy, Autophagy/*drug effects, Butyrate, Butyrates/*pharmacology, Butyric Acid/pharmacology, Caspase 3/genetics/metabolism, Cell Differentiation/drug effects, Colon cancer, Colonic Neoplasms/*pathology, Differentiation, Docosahexaenoic acid, Docosahexaenoic Acids/*pharmacology, HCT116 Cells, HT29 Cells, Humans, Mitochondria/drug effects/metabolism, PPAR gamma/genetics/*metabolism, PPARγ
@article{tylichova_activation_2017,
title = {Activation of autophagy and PPARγ protect colon cancer cells against apoptosis induced by interactive effects of butyrate and DHA in a cell type-dependent manner: The role of cell differentiation.},
author = {Zuzana Tylichová and Nicol Straková and Jan Vondráček and Alena Hyršlová Vaculová and Alois Kozubík and Jiřina Hofmanová},
doi = {10.1016/j.jnutbio.2016.09.006},
issn = {1873-4847 0955-2863},
year = {2017},
date = {2017-01-01},
journal = {The Journal of nutritional biochemistry},
volume = {39},
pages = {145–155},
abstract = {The short-chain and n-3 polyunsaturated fatty acids exhibit anticancer properties, and they may mutually interact within the colon. However, the molecular mechanisms of their action in colon cancer cells are still not fully understood. Our study focused on the mechanisms responsible for the diverse effects of sodium butyrate (NaBt), in particular when interacting with docosahexaenoic acid (DHA), in distinct colon cancer cell types, in which NaBt either induces cell differentiation or activates programmed cell death involving mitochondrial pathway. NaBt activated autophagy both in HT-29 cells, which are sensitive to induction of differentiation, and in nondifferentiating HCT-116 cells. However, autophagy supported cell survival only in HT-29 cells. Combination of NaBt with DHA-promoted cell death, especially in HCT-116 cells and after longer time intervals. The inhibition of autophagy both attenuated differentiation and enhanced apoptosis in HT-29 cells treated with NaBt and DHA, but it had no effect in HCT-116 cells. NaBt, especially in combination with DHA, activated PPARγ in both cell types. PPARγ silencing decreased differentiation and increased apoptosis only in HT-29 cells, therefore we verified the role of caspases in apoptosis, differentiation and also PPARγ activity using a pan-caspase inhibitor. In summary, our data suggest that diverse responses of colon cancer cells to fatty acids may rely on their sensitivity to differentiation, which may in turn depend on distinct engagement of autophagy, caspases and PPARγ. These results contribute to understanding of mechanisms underlying differential effects of NaBt, when interacting with other dietary fatty acids, in colon cancer cells.},
note = {Place: United States},
keywords = {Antineoplastic Agents/pharmacology, Apoptosis/*drug effects, Autophagy, Autophagy/*drug effects, Butyrate, Butyrates/*pharmacology, Butyric Acid/pharmacology, Caspase 3/genetics/metabolism, Cell Differentiation/drug effects, Colon cancer, Colonic Neoplasms/*pathology, Differentiation, Docosahexaenoic acid, Docosahexaenoic Acids/*pharmacology, HCT116 Cells, HT29 Cells, Humans, Mitochondria/drug effects/metabolism, PPAR gamma/genetics/*metabolism, PPARγ},
pubstate = {published},
tppubtype = {article}
}
The short-chain and n-3 polyunsaturated fatty acids exhibit anticancer properties, and they may mutually interact within the colon. However, the molecular mechanisms of their action in colon cancer cells are still not fully understood. Our study focused on the mechanisms responsible for the diverse effects of sodium butyrate (NaBt), in particular when interacting with docosahexaenoic acid (DHA), in distinct colon cancer cell types, in which NaBt either induces cell differentiation or activates programmed cell death involving mitochondrial pathway. NaBt activated autophagy both in HT-29 cells, which are sensitive to induction of differentiation, and in nondifferentiating HCT-116 cells. However, autophagy supported cell survival only in HT-29 cells. Combination of NaBt with DHA-promoted cell death, especially in HCT-116 cells and after longer time intervals. The inhibition of autophagy both attenuated differentiation and enhanced apoptosis in HT-29 cells treated with NaBt and DHA, but it had no effect in HCT-116 cells. NaBt, especially in combination with DHA, activated PPARγ in both cell types. PPARγ silencing decreased differentiation and increased apoptosis only in HT-29 cells, therefore we verified the role of caspases in apoptosis, differentiation and also PPARγ activity using a pan-caspase inhibitor. In summary, our data suggest that diverse responses of colon cancer cells to fatty acids may rely on their sensitivity to differentiation, which may in turn depend on distinct engagement of autophagy, caspases and PPARγ. These results contribute to understanding of mechanisms underlying differential effects of NaBt, when interacting with other dietary fatty acids, in colon cancer cells.