Disease modeling following organoid-based expansion of airway epithelial cells

Evelien Eenjes; Sander van Riet; Andre A Kroon; Annelies M Slats; P Padmini S J Khedoe; Anne Boerema-de Munck; Marjon Buscop-van Kempen; Dennis K Ninaber; Irwin K M Reiss; Hans Clevers; Robbert J Rottier; Pieter S Hiemstra

doi:10.1152/ajplung.00234.2020

Disease modeling following organoid-based expansion of airway epithelial cells

Evelien Eenjes, Sander van Riet, Andre A Kroon, Annelies M Slats, P Padmini S J Khedoe, Anne Boerema-de Munck, Marjon Buscop-van Kempen, Dennis K Ninaber, Irwin K M Reiss, Hans Clevers, Robbert J Rottier, Pieter S Hiemstra

Hubrecht Institute

Onderzoeksoutput: Bijdrage aan wetenschappelijk tijdschrift/periodieke uitgave › Artikel › Wetenschappelijk › peer review

21 Citaten (Scopus)

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Air-liquid interface (ALI) cultures are frequently used in lung research but require substantial cell numbers that cannot readily be obtained from patients. We explored whether organoid expansion [three-dimensional (3D)] can be used to establish ALI cultures from clinical samples with low epithelial cell numbers. Airway epithelial cells were obtained from tracheal aspirates (TA) from preterm newborns and from bronchoalveolar lavage (BAL) or bronchial tissue (BT) from adults. TA and BAL cells were 3D-expanded, whereas cells from BT were expanded in 3D and 2D. Following expansion, cells were cultured at ALI to induce differentiation. The impact of cell origin and 2D or 3D expansion was assessed with respect to 1) cellular composition, 2) response to cigarette smoke exposure, and 3) effect of Notch inhibition or IL-13 stimulation on cellular differentiation. We established well-differentiated ALI cultures from all samples. Cellular compositions (basal, ciliated, and goblet cells) were comparable. All 3D-expanded cultures showed a similar stress response following cigarette smoke exposure but differed from the 2D-expanded cultures. Higher peak levels of antioxidant genes HMOX1 and NQO1 and a more rapid return to baseline, and a lower unfolded protein response was observed after cigarette smoke exposure in 3D-derived cultures compared to 2D-derived cultures. In addition, TA- and BAL-derived cultures were less sensitive to modulation by DAPT or IL-13 than BT-derived cultures. Organoid-based expansion of clinical samples with low cell numbers, such as TA from preterm newborns is a valid method and tool to establish ALI cultures.

Originele taal-2	Engels
Pagina's (van-tot)	L775-L786
Tijdschrift	American journal of physiology. Lung cellular and molecular physiology
Volume	321
Nummer van het tijdschrift	4
DOI's	https://doi.org/10.1152/ajplung.00234.2020
Status	Gepubliceerd - 01 okt. 2021

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10.1152/ajplung.00234.2020

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Eenjes, E., van Riet, S., Kroon, A. A., Slats, A. M., Khedoe, P. P. S. J., Boerema-de Munck, A., Buscop-van Kempen, M., Ninaber, D. K., Reiss, I. K. M., Clevers, H., Rottier, R. J., & Hiemstra, P. S. (2021). Disease modeling following organoid-based expansion of airway epithelial cells. American journal of physiology. Lung cellular and molecular physiology, 321(4), L775-L786. https://doi.org/10.1152/ajplung.00234.2020

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abstract = "Air-liquid interface (ALI) cultures are frequently used in lung research but require substantial cell numbers that cannot readily be obtained from patients. We explored whether organoid expansion [three-dimensional (3D)] can be used to establish ALI cultures from clinical samples with low epithelial cell numbers. Airway epithelial cells were obtained from tracheal aspirates (TA) from preterm newborns and from bronchoalveolar lavage (BAL) or bronchial tissue (BT) from adults. TA and BAL cells were 3D-expanded, whereas cells from BT were expanded in 3D and 2D. Following expansion, cells were cultured at ALI to induce differentiation. The impact of cell origin and 2D or 3D expansion was assessed with respect to 1) cellular composition, 2) response to cigarette smoke exposure, and 3) effect of Notch inhibition or IL-13 stimulation on cellular differentiation. We established well-differentiated ALI cultures from all samples. Cellular compositions (basal, ciliated, and goblet cells) were comparable. All 3D-expanded cultures showed a similar stress response following cigarette smoke exposure but differed from the 2D-expanded cultures. Higher peak levels of antioxidant genes HMOX1 and NQO1 and a more rapid return to baseline, and a lower unfolded protein response was observed after cigarette smoke exposure in 3D-derived cultures compared to 2D-derived cultures. In addition, TA- and BAL-derived cultures were less sensitive to modulation by DAPT or IL-13 than BT-derived cultures. Organoid-based expansion of clinical samples with low cell numbers, such as TA from preterm newborns is a valid method and tool to establish ALI cultures.",

keywords = "Adult, Bronchi/cytology, Bronchoalveolar Lavage Fluid/cytology, Cell Culture Techniques, Cell Differentiation/physiology, Cells, Cultured, Epithelial Cells/cytology, Heme Oxygenase-1/metabolism, Humans, Infant, Newborn, Interleukin-13/metabolism, NAD(P)H Dehydrogenase (Quinone)/metabolism, Organoids/cytology, Receptors, Notch/antagonists & inhibitors, Respiratory Mucosa/cytology, Smoke/adverse effects, Tobacco Products/adverse effects, Unfolded Protein Response/drug effects",

author = "Evelien Eenjes and {van Riet}, Sander and Kroon, {Andre A} and Slats, {Annelies M} and Khedoe, {P Padmini S J} and {Boerema-de Munck}, Anne and {Buscop-van Kempen}, Marjon and Ninaber, {Dennis K} and Reiss, {Irwin K M} and Hans Clevers and Rottier, {Robbert J} and Hiemstra, {Pieter S}",

year = "2021",

month = oct,

day = "1",

doi = "10.1152/ajplung.00234.2020",

language = "English",

volume = "321",

pages = "L775--L786",

journal = "American journal of physiology. Lung cellular and molecular physiology",

issn = "1040-0605",

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Eenjes, E, van Riet, S, Kroon, AA, Slats, AM, Khedoe, PPSJ, Boerema-de Munck, A, Buscop-van Kempen, M, Ninaber, DK, Reiss, IKM, Clevers, H, Rottier, RJ & Hiemstra, PS 2021, 'Disease modeling following organoid-based expansion of airway epithelial cells', American journal of physiology. Lung cellular and molecular physiology, vol. 321, nr. 4, blz. L775-L786. https://doi.org/10.1152/ajplung.00234.2020

Disease modeling following organoid-based expansion of airway epithelial cells. / Eenjes, Evelien; van Riet, Sander; Kroon, Andre A et al.
In: American journal of physiology. Lung cellular and molecular physiology, Vol. 321, Nr. 4, 01.10.2021, blz. L775-L786.

Onderzoeksoutput: Bijdrage aan wetenschappelijk tijdschrift/periodieke uitgave › Artikel › Wetenschappelijk › peer review

TY - JOUR

T1 - Disease modeling following organoid-based expansion of airway epithelial cells

AU - Eenjes, Evelien

AU - van Riet, Sander

AU - Kroon, Andre A

AU - Slats, Annelies M

AU - Khedoe, P Padmini S J

AU - Boerema-de Munck, Anne

AU - Buscop-van Kempen, Marjon

AU - Ninaber, Dennis K

AU - Reiss, Irwin K M

AU - Clevers, Hans

AU - Rottier, Robbert J

AU - Hiemstra, Pieter S

PY - 2021/10/1

Y1 - 2021/10/1

N2 - Air-liquid interface (ALI) cultures are frequently used in lung research but require substantial cell numbers that cannot readily be obtained from patients. We explored whether organoid expansion [three-dimensional (3D)] can be used to establish ALI cultures from clinical samples with low epithelial cell numbers. Airway epithelial cells were obtained from tracheal aspirates (TA) from preterm newborns and from bronchoalveolar lavage (BAL) or bronchial tissue (BT) from adults. TA and BAL cells were 3D-expanded, whereas cells from BT were expanded in 3D and 2D. Following expansion, cells were cultured at ALI to induce differentiation. The impact of cell origin and 2D or 3D expansion was assessed with respect to 1) cellular composition, 2) response to cigarette smoke exposure, and 3) effect of Notch inhibition or IL-13 stimulation on cellular differentiation. We established well-differentiated ALI cultures from all samples. Cellular compositions (basal, ciliated, and goblet cells) were comparable. All 3D-expanded cultures showed a similar stress response following cigarette smoke exposure but differed from the 2D-expanded cultures. Higher peak levels of antioxidant genes HMOX1 and NQO1 and a more rapid return to baseline, and a lower unfolded protein response was observed after cigarette smoke exposure in 3D-derived cultures compared to 2D-derived cultures. In addition, TA- and BAL-derived cultures were less sensitive to modulation by DAPT or IL-13 than BT-derived cultures. Organoid-based expansion of clinical samples with low cell numbers, such as TA from preterm newborns is a valid method and tool to establish ALI cultures.

AB - Air-liquid interface (ALI) cultures are frequently used in lung research but require substantial cell numbers that cannot readily be obtained from patients. We explored whether organoid expansion [three-dimensional (3D)] can be used to establish ALI cultures from clinical samples with low epithelial cell numbers. Airway epithelial cells were obtained from tracheal aspirates (TA) from preterm newborns and from bronchoalveolar lavage (BAL) or bronchial tissue (BT) from adults. TA and BAL cells were 3D-expanded, whereas cells from BT were expanded in 3D and 2D. Following expansion, cells were cultured at ALI to induce differentiation. The impact of cell origin and 2D or 3D expansion was assessed with respect to 1) cellular composition, 2) response to cigarette smoke exposure, and 3) effect of Notch inhibition or IL-13 stimulation on cellular differentiation. We established well-differentiated ALI cultures from all samples. Cellular compositions (basal, ciliated, and goblet cells) were comparable. All 3D-expanded cultures showed a similar stress response following cigarette smoke exposure but differed from the 2D-expanded cultures. Higher peak levels of antioxidant genes HMOX1 and NQO1 and a more rapid return to baseline, and a lower unfolded protein response was observed after cigarette smoke exposure in 3D-derived cultures compared to 2D-derived cultures. In addition, TA- and BAL-derived cultures were less sensitive to modulation by DAPT or IL-13 than BT-derived cultures. Organoid-based expansion of clinical samples with low cell numbers, such as TA from preterm newborns is a valid method and tool to establish ALI cultures.

KW - Adult

KW - Bronchi/cytology

KW - Bronchoalveolar Lavage Fluid/cytology

KW - Cell Culture Techniques

KW - Cell Differentiation/physiology

KW - Cells, Cultured

KW - Epithelial Cells/cytology

KW - Heme Oxygenase-1/metabolism

KW - Humans

KW - Infant, Newborn

KW - Interleukin-13/metabolism

KW - NAD(P)H Dehydrogenase (Quinone)/metabolism

KW - Organoids/cytology

KW - Receptors, Notch/antagonists & inhibitors

KW - Respiratory Mucosa/cytology

KW - Smoke/adverse effects

KW - Tobacco Products/adverse effects

KW - Unfolded Protein Response/drug effects

U2 - 10.1152/ajplung.00234.2020

DO - 10.1152/ajplung.00234.2020

M3 - Article

C2 - 34378410

SN - 1040-0605

VL - 321

SP - L775-L786

JO - American journal of physiology. Lung cellular and molecular physiology

JF - American journal of physiology. Lung cellular and molecular physiology

IS - 4

ER -

Disease modeling following organoid-based expansion of airway epithelial cells

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