L-cysteine or vitamin C influence cellular growth and prolong survival of normal adult human lung tissue in culture

Human pluripotent stem cell (hPSC) derived tissues often remain developmentally immature in vitro, and become more adult-like in their structure, cellular diversity and function following transplantation into immunocompromised mice. Previously we have demonstrated that hPSC-derived human lung organoids (HLOs) resembled human fetal lung tissue in vitro (<xref ref-type="bibr" rid="bib10">Dye et al., 2015</xref>). Here we show that HLOs required a bioartificial microporous poly(lactide-co-glycolide) (PLG) scaffold niche for successful engraftment, long-term survival, and maturation of lung epithelium in vivo. Analysis of scaffold-grown transplanted tissue showed airway-like tissue with enhanced epithelial structure and organization compared to HLOs grown in vitro. By further comparing in vitro and in vivo grown HLOs with fetal and adult human lung tissue, we found that in vivo transplanted HLOs had improved cellular differentiation of secretory lineages that is reflective of differences between fetal and adult tissue, resulting in airway-like structures that were remarkably similar to the native adult human lung.

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Engraftment of Adult Human Lung Tissue in Nonobese Diabetic/Severe Combined Immunodeficient Mice: A Novel Lung Epithelial Regeneration Model

Pathobiology ◽

10.1159/000074422 ◽

2004 ◽

Vol 71 (2) ◽

pp. 93-102 ◽

Cited By ~ 2

Author(s):

Hiroyuki Yonou ◽

Tomoyuki Yokose ◽

Takeshi Yoshikawa ◽

Naoki Kanomata ◽

Tomoyuki Kamijo ◽

...

Keyword(s):

Lung Tissue ◽

Human Lung ◽

Human Lung Tissue ◽

Immunodeficient Mice ◽

Epithelial Regeneration ◽

Adult Human ◽

Nonobese Diabetic ◽

Lung Epithelial ◽

Adult Human Lung

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Quantitative study of endocrine cells immunoreactive for calcitonin in the normal adult human lung.

Thorax ◽

10.1136/thx.40.11.866 ◽

1985 ◽

Vol 40 (11) ◽

pp. 866-869 ◽

Cited By ~ 19

Author(s):

J R Gosney ◽

M C Sissons ◽

J A O'Malley

Keyword(s):

Quantitative Study ◽

Endocrine Cells ◽

Human Lung ◽

Normal Adult ◽

Adult Human ◽

Adult Human Lung

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Mast Cell Heterogeneity in Human Lung Tissue

Clinical Science ◽

10.1042/cs0770297 ◽

1989 ◽

Vol 77 (3) ◽

pp. 297-304 ◽

Cited By ~ 10

Author(s):

F. J. Van Overveld ◽

L. A. M. J. Houben ◽

F. E. M. Schmitz du Moulin ◽

P. L. B. Bruijnzeel ◽

J. A. M. Raaijmakers ◽

...

Keyword(s):

Mast Cell ◽

Mast Cells ◽

Alcian Blue ◽

Lung Tissue ◽

Human Lung ◽

Immunoglobulin E ◽

Prostaglandin D2 ◽

Leukotriene C4 ◽

Human Lung Tissue ◽

No Release

1. In this study mast cells were found to comprise 2.1% of total cells recovered by enzymatic digestion of human lung tissue. 2. This mast cell population consisted of 79% formalin-sensitive, Alcian Blue-positive mast cells and 21% formalin-insensitive, Alcian Blue-positive mast cells. 3. By the use of centrifugal elutriation and subsequent Percoll gradient centrifugation, separate mixed cell populations could be obtained in which the mast cell constituents were either of the formalin-sensitive or -insensitive type. 4. Cell suspensions in which formalin-sensitive cells comprised 97% of mast cells contained approximately 1.34 pg of histamine per mast cell, whereas in preparations in which mast cells were 84% formalin-resistant the histamine content was approximately 4.17 pg of histamine per mast cell. 5. The histamine release upon anti-immunoglobulin E challenge of formalin-sensitive mast cells was greater than the release by formalin-insensitive mast cells. 6. After challenge with opsonized zymosan, only formalin-sensitive mast cells were able to release histamine. 7. Leukotriene C4 release was observed when formalin-sensitive mast cells were challenged with antiimmunoglobulin E. Formalin-insensitive mast cells showed no release of leukotriene C4. 8. Prostaglandin D2 release was observed when formalin-insensitive mast cells were challenged with antiimmunoglobulin E. Formalin-sensitive mast cells showed no release of prostaglandin D2.

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The Glucocorticosteroid, Budesonide, Partially Blocks Histamine Release from Human Lung Tissue in Vitro

Allergy ◽

10.1111/j.1398-9995.1986.tb00307.x ◽

1986 ◽

Vol 41 (5) ◽

pp. 319-326 ◽

Cited By ~ 6

Author(s):

H. Bergstrand ◽

B. Lundquist ◽

B.-Å. Petersson

Keyword(s):

Histamine Release ◽

Lung Tissue ◽

Human Lung ◽

Human Lung Tissue

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Antiinflammatory steroids inhibit granulocyte/macrophage colony-stimulating factor production by human lung tissue

Lung ◽

10.1007/bf00185082 ◽

1994 ◽

Vol 172 (2) ◽

Cited By ~ 15

Author(s):

M. Kato ◽

R.P. Schleimer

Keyword(s):

Lung Tissue ◽

Human Lung ◽

Colony Stimulating Factor ◽

Human Lung Tissue ◽

Factor Production ◽

Macrophage Colony Stimulating Factor ◽

Macrophage Colony ◽

Antiinflammatory Steroids ◽

Stimulating Factor

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Human Lung Tissue Explants Reveal Novel Interactions during Legionella pneumophila Infections

Infection and Immunity ◽

10.1128/iai.00703-13 ◽

2013 ◽

Vol 82 (1) ◽

pp. 275-285 ◽

Cited By ~ 35

Author(s):

Jens Jäger ◽

Sebastian Marwitz ◽

Jana Tiefenau ◽

Janine Rasch ◽

Olga Shevchuk ◽

...

Keyword(s):

Lung Tissue ◽

Legionella Pneumophila ◽

Human Lung ◽

Transcriptional Response ◽

Human Infection ◽

Bacterial Invasion ◽

Human Lung Tissue ◽

Content Type ◽

Tissue Explants ◽

Legionnaires Disease

ABSTRACTHistological and clinical investigations describe late stages of Legionnaires' disease but cannot characterize early events of human infection. Cellular or rodent infection models lack the complexity of tissue or have nonhuman backgrounds. Therefore, we developed and applied a novel model forLegionella pneumophilainfection comprising living human lung tissue. We stimulated lung explants withL. pneumophilastrains and outer membrane vesicles (OMVs) to analyze tissue damage, bacterial replication, and localization as well as the transcriptional response of infected tissue. Interestingly, we found that extracellular adhesion ofL. pneumophilato the entire alveolar lining precedes bacterial invasion and replication in recruited macrophages. In contrast, OMVs predominantly bound to alveolar macrophages. Specific damage to septa and epithelia increased over 48 h and was stronger in wild-type-infected and OMV-treated samples than in samples infected with the replication-deficient, type IVB secretion-deficient DotA−strain. Transcriptome analysis of lung tissue explants revealed a differential regulation of 2,499 genes after infection. The transcriptional response included the upregulation of uteroglobin and the downregulation of the macrophage receptor with collagenous structure (MARCO). Immunohistochemistry confirmed the downregulation of MARCO at sites of pathogen-induced tissue destruction. Neither host factor has ever been described in the context ofL. pneumophilainfections. This work demonstrates that the tissue explant model reproduces realistic features of Legionnaires' disease and reveals new functions for bacterial OMVs during infection. Our model allows us to characterize early steps of human infection which otherwise are not feasible for investigations.

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Preparation of Single Cell Suspension from Human Lung Tissue v1

10.17504/protocols.io.bwr9pd96 ◽

2021 ◽

Author(s):

Steven B. Wells ◽

Peter A. Szabo ◽

Basak Ural ◽

Maya M.L. Poon

Keyword(s):

Epithelial Cells ◽

Cell Suspension ◽

Single Cell ◽

Lung Tissue ◽

Immune Cells ◽

Human Lung ◽

Dilution Factor ◽

Single Cell Suspension ◽

Human Lung Tissue ◽

Defined Media

This protocol describes a method for the isolation of the immune cells, structural and epithelial cells, and progenitors from human lung sections of about two grams. By providing defined media formulations, volumes at each step, and a defined dilution factor for density centrifugation, it yields consistent single-cell suspensions across samples.

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