scholarly journals Self-organized stem cell-derived human lung buds with proximo-distal patterning and novel targets of SARS-CoV-2

2021 ◽  
Author(s):  
E.A. Rosado-Olivieri ◽  
B. Razooky ◽  
H.-H. Hoffmann ◽  
R. De Santis ◽  
C.M. Rice ◽  
...  
Keyword(s):  
Stem Cells ◽  
Lung Tissue ◽  
Neutralizing Antibodies ◽  
Human Lung ◽  
Cell Type ◽  
Alveolar Cells ◽  
Human Lung Tissue ◽  
Alveolar Tissue

AbstractSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of the global COVID-19 pandemic and the lack of therapeutics hinders pandemic control1–2. Although lung disease is the primary clinical outcome in COVID-19 patients1–3, how SARS-CoV-2 induces tissue pathology in the lung remains elusive. Here we describe a high-throughput platform to generate tens of thousands of self-organizing, nearly identical, and genetically matched human lung buds derived from human pluripotent stem cells (hPSCs) cultured on micropatterned substrates. Strikingly, in vitro-derived human lung buds resemble fetal human lung tissue and display in vivo-like proximo-distal coordination of alveolar and airway tissue differentiation whose 3D epithelial self-organization is directed by the levels of KGF. Single-cell transcriptomics unveiled the cellular identities of airway and alveolar tissue and the differentiation of WNThi cycling alveolar stem cells, a human-specific lung cell type4. These synthetic human lung buds are susceptible to infection by SARS-CoV-2 and endemic coronaviruses and can be used to track cell type-dependent susceptibilities to infection, intercellular transmission and cytopathology in airway and alveolar tissue in individual lung buds. Interestingly, we detected an increased susceptibility to infection in alveolar cells and identified cycling alveolar stem cells as targets of SARS-CoV-2. We used this platform to test neutralizing antibodies isolated from convalescent plasma that efficiently blocked SARS-CoV-2 infection and intercellular transmission. Our platform offers unlimited, rapid and scalable access to disease-relevant lung tissue that recapitulate key hallmarks of human lung development and can be used to track SARS-CoV-2 infection and identify candidate therapeutics for COVID-19.

scholarly journals A bioengineered niche promotes in vivo engraftment and maturation of pluripotent stem cell derived human lung organoids

eLife ◽  
2016 ◽  
Vol 5 ◽  
Author(s):  
Briana R Dye ◽  
Priya H Dedhia ◽  
Alyssa J Miller ◽  
Melinda S Nagy ◽  
Eric S White ◽  
...  
Keyword(s):  
Stem Cell ◽  
Lung Tissue ◽  
Pluripotent Stem Cell ◽  
Human Lung ◽  
Human Lung Tissue ◽  
Term Survival ◽  
Adult Human ◽  
Adult Human Lung

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.

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

Allergy ◽  
1986 ◽  
Vol 41 (5) ◽  
pp. 319-326 ◽  
Author(s):  
H. Bergstrand ◽  
B. Lundquist ◽  
B.-Å. Petersson
Keyword(s):  
Histamine Release ◽  
Lung Tissue ◽  
Human Lung ◽  
Human Lung Tissue

scholarly journals Native matrix-based human lung alveolar tissue model in vitro: studies of the reparatory actions of mesenchymal stem cells

2016 ◽  
Vol 69 (1) ◽  
pp. 1-17 ◽  
Author(s):  
Ieva Bruzauskaite ◽  
Jovile Raudoniute ◽  
Jaroslav Denkovskij ◽  
Edvardas Bagdonas ◽  
Sandra Meidute-Abaraviciene ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Human Lung ◽  
In Vitro Studies ◽  
Tissue Model ◽  
Alveolar Tissue

scholarly journals A labelled-ubiquicidin antimicrobial peptide for immediate in situ optical detection of live bacteria in human alveolar lung tissue

2015 ◽  
Vol 6 (12) ◽  
pp. 6971-6979 ◽  
Author(s):  
Ahsan R. Akram ◽  
Nicolaos Avlonitis ◽  
Annamaria Lilienkampf ◽  
Ana M. Perez-Lopez ◽  
Neil McDonald ◽  
...  
Keyword(s):  
Antimicrobial Peptide ◽  
Lung Tissue ◽  
Human Lung ◽  
Optical Detection ◽  
Human Lung Tissue ◽  
Bacterial Detection ◽  
Live Bacteria

A fluorescently labelled ubiquicidin peptide enables bacterial detection in human lung tissuein vitro.

scholarly journals Distribution of inhaled fluticasone propionate between human lung tissue and serum in vivo

1997 ◽  
Vol 10 (7) ◽  
pp. 1496-1499 ◽  
Author(s):  
N. Esmailpour ◽  
P. Högger ◽  
K.F. Rabe ◽  
U. Heitmann ◽  
M. Nakashima ◽  
...  
Keyword(s):  
Fluticasone Propionate ◽  
Lung Tissue ◽  
Human Lung ◽  
Human Lung Tissue

Light distribution in human lung tissue at 413.1 nm in vitro

1998 ◽  
Author(s):  
Zhiwei Huang ◽  
Chee T. Chia ◽  
Cheong Hoong Diong ◽  
Sing Lee ◽  
Wei-Ming Zheng ◽  
...  
Keyword(s):  
Lung Tissue ◽  
Human Lung ◽  
Light Distribution ◽  
Human Lung Tissue

High-Resolution CT Findings of Leukemia Pulmonary Infiltration and Chemotherapy Outcome and In Vitro Study of Human Lung Tissue

2021 ◽  
Vol 11 (2) ◽  
pp. 360-369
Author(s):  
Caide Xie ◽  
Tianjing Zhao ◽  
Liang Fang
Keyword(s):  
High Resolution ◽  
Lung Tissue ◽  
Human Lung ◽  
Ct Imaging ◽  
Imaging Features ◽  
Human Lung Tissue ◽  
High Resolution Ct ◽  
Ct Findings ◽  
Pulmonary Infiltration

In order to explore the high-resolution CT findings of leukemia pulmonary infiltration and chemotherapy outcomes and the in vitro study of human lung tissue, this paper selected a total of 120 clinically or surgically confirmed leukemia patients at the designated hospital of the study from December 2014 to December 2018, and divided them into three groups according to the random number table method: pulmonary infiltration group, chemotherapy outcome group and in vitro study group, with 40 cases in each group. The CT imaging features of the three groups of patients were observed and summarized respectively; the anomalous evaluation indexes of pulmonary parenchyma tissue abnormalities included CT halo sign, air crescent sign, lung segment consolidation, bronchial vascular bundle and nodules; the CT abnormalities such as thickening of the interlobular septum, bronchial interstitial thickening, nodular shadow, ground glassy change, and air cavity consolidation were selected as observation indicators. The results show that all cases have multiple solid nodules or multiple plaques, varying in number, size and distribution, in which 13 cases have multiple patchy shadows, 9 cases have multiple knots and 11 cases have multiple plaques and nodules; lesions are mainly distributed along the bronchial vessels in 21 cases, and 9 cases are along the center of the small leaves and 5 cases are randomly distributed; there are 13 cases that have frosted glass, in which 4 cases with pleural effusion, 9 cases with mold infection, show multiple patchy shadows with halo signs and layered mold balls. In summary, leukemia pulmonary infiltration has polymorphic high-resolution CT findings and chemotherapy outcomes; high-resolution CT imaging and in vitro studies of human lung tissue have important clinical and pathological research value for leukemia infiltration and chemotherapy outcome. The results of this study provide a reference for the further researches on high-resolution CT findings of pulmonary infiltration and chemotherapy outcomes and in vitro studies of human lung tissue.

scholarly journals Acute SARS-CoV-2 Infection is Highly Cytopathic, Elicits a Robust Innate Immune Response and is Efficiently Prevented by EIDD-2801

2020 ◽  
Author(s):  
Angela Wahl ◽  
Lisa Gralinski ◽  
Claire Johnson ◽  
Wenbo Yao ◽  
Martina Kovarova ◽  
...  
Keyword(s):  
Lung Tissue ◽  
Human Lung ◽  
Lung Epithelial Cells ◽  
Type I ◽  
Human Lung Tissue ◽  
Type Ii Pneumocytes ◽  
Bona Fide ◽  
Human Coronaviruses ◽  
Exposure Prophylaxis

Abstract All known recently emerged human coronaviruses likely originated in bats. Here, we used a single experimental platform based on human lung-only mice (LoM) to demonstrate efficient in vivo replication of all recently emerged human coronaviruses (SARS-CoV, MERS-CoV, SARS-CoV-2) and two highly relevant endogenous pre-pandemic SARS-like bat coronaviruses. Virus replication in this model occurs in bona fide human lung tissue and does not require any type of adaptation of the virus or the host. Our results indicate that bats harbor endogenous coronaviruses capable of direct transmission into humans. Further detailed analysis of pandemic SARS-CoV-2 in vivo infection of LoM human lung tissue showed predominant infection of human lung epithelial cells, including type II pneumocytes present in alveoli and ciliated airway cells. Acute SARS-CoV-2 infection was highly cytopathic and induced a robust and sustained Type I interferon and inflammatory cytokine/chemokine response. Finally, we evaluated a pre-exposure prophylaxis strategy for coronavirus infection. Our results show that prophylactic administration of EIDD-2801, an oral broad spectrum antiviral currently in phase II clinical trials for the treatment of COVID-19, dramatically prevented SARS-CoV-2 infection in vivo and thus has significant potential for the prevention and treatment of COVID-19.

scholarly journals Electron microscopic study of human lung tissue after in vitro exposure to elastase.

1993 ◽  
Vol 41 (6) ◽  
pp. 851-866 ◽  
Author(s):  
S M Morris ◽  
P J Stone ◽  
G L Snider
Keyword(s):  
Animal Models ◽  
Lung Tissue ◽  
Human Lung ◽  
Basement Membranes ◽  
Morphological Evidence ◽  
Elastic Fibers ◽  
Human Neutrophil Elastase ◽  
Human Lung Tissue ◽  
Thin Sections

Much of the experimental evidence supporting the hypothesis that pulmonary emphysema results from an imbalance between elastases and anti-elastases in the lung comes from animal models. The present study was designed to examine the effects on human lung tissue of the two elastases that have been most widely used to produce these animal models. Lung tissue was exposed in vitro to human neutrophil elastase (HNE) or porcine pancreatic elastase (PPE). Although both enzymes solubilized protein at similar rates, PPE solubilized elastin five times faster than did HNE. Ultrastructurally, HNE-exposed tissue exhibited fewer damaged elastic fibers as well as some fibers that were damaged at the edges, whereas the interior of the fiber appeared intact. Elastic fibers showing damage only at the periphery were not seen in tissue exposed to PPE. Immunocytochemical studies in which antibodies to HNE and PPE were applied to thin sections of Lowicryl-embedded tissue indicated that both of these elastases could be detected in association with elastic fibers, but only in areas of the fiber that showed morphological evidence of elastase injury. Both HNE and PPE removed fibronectin from basement membranes (as determined by loss of binding of fibronectin antibodies after exposure to elastase), but neither elastase was detected on basement membrane. Loss of epithelial cells usually accompanied elastic fiber damage by HNE but not PPE.

scholarly journals Development of anEx VivoTissue Platform To Study the Human Lung Response to Coxiella burnetii

2016 ◽  
Vol 84 (5) ◽  
pp. 1438-1445 ◽  
Author(s):  
Joseph G. Graham ◽  
Caylin G. Winchell ◽  
Richard C. Kurten ◽  
Daniel E. Voth
Keyword(s):  
Coxiella Burnetii ◽  
Lung Tissue ◽  
Human Lung ◽  
Q Fever ◽  
Ex Vivo ◽  
Parasitophorous Vacuole ◽  
Inflammasome Activation ◽  
Human Lung Tissue ◽  
Content Type

Coxiella burnetiiis an intracellular bacterial pathogen that causes human Q fever, an acute debilitating flu-like illness that can also present as chronic endocarditis. Disease typically occurs following inhalation of contaminated aerosols, resulting in an initial pulmonary infection. In human cells,C. burnetiigenerates a replication niche termed the parasitophorous vacuole (PV) by directing fusion with autophagosomes and lysosomes.C. burnetiirequires this lysosomal environment for replication and uses a Dot/Icm type IV secretion system to generate the large PV. However, we do not understand howC. burnetiievades the intracellular immune surveillance that triggers an inflammatory response. We recently characterized human alveolar macrophage (hAM) infectionin vitroand found that avirulentC. burnetiitriggers sustained interleukin-1β (IL-1β) production. Here, we evaluated infection ofex vivohuman lung tissue, defining a valuable approach for characterizingC. burnetiiinteractions with a human host. Within whole lung tissue,C. burnetiipreferentially replicated in hAMs. Additionally, IL-1β production correlated with formation of an apoptosis-associated speck-like protein containing a caspase activation and recruitment domain (ASC)-dependent inflammasome in response to infection. We also assessed potential activation of a human-specific noncanonical inflammasome and found that caspase-4 and caspase-5 are processed during infection. Interestingly, although inflammasome activation is closely linked to pyroptosis, lytic cell death did not occur followingC. burnetii-triggered inflammasome activation, indicating an atypical response after intracellular detection. Together, these studies provide a novel platform for studying the human innate immune response toC. burnetii.

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