scholarly journals In Vitro Models to Study Human Lung Development, Disease and Homeostasis

Physiology ◽  
2017 ◽  
Vol 32 (3) ◽  
pp. 246-260 ◽  
Author(s):  
Alyssa J. Miller ◽  
Jason R. Spence
Keyword(s):  
Animal Models ◽  
Lung Development ◽  
Human Lung ◽  
In Vitro Models ◽  
Structure And Function ◽  
Tissue Cell ◽  
Main Function ◽  
Human Pluripotent Stem Cell ◽  
And Function

The main function of the lung is to support gas exchange, and defects in lung development or diseases affecting the structure and function of the lung can have fatal consequences. Most of what we currently understand about human lung development and disease has come from animal models. However, animal models are not always fully able to recapitulate human lung development and disease, highlighting an area where in vitro models of the human lung can compliment animal models to further understanding of critical developmental and pathological mechanisms. This review will discuss current advances in generating in vitro human lung models using primary human tissue, cell lines, and human pluripotent stem cell derived lung tissue, and will discuss crucial next steps in the field.

In vitro models of differentiated sertoli cell structure and function

1988 ◽  
Vol 24 (6) ◽  
pp. 550-557 ◽  
Author(s):  
Mark A. Hadley ◽  
Stephen W. Byers ◽  
Carlos A. Suárez-Quian ◽  
daniel Djakiew ◽  
Martin Dym
Keyword(s):  
Sertoli Cell ◽  
Cell Structure ◽  
In Vitro Models ◽  
Structure And Function ◽  
And Function

scholarly journals Use of three-dimensional organoids and lung-on-a-chip methods to study lung development, regeneration and disease

2018 ◽  
Vol 52 (5) ◽  
pp. 1800876 ◽  
Author(s):  
Konstantinos Gkatzis ◽  
Sara Taghizadeh ◽  
Dongeun Huh ◽  
Didier Y.R. Stainier ◽  
Saverio Bellusci
Keyword(s):  
Pluripotent Stem Cells ◽  
Lung Development ◽  
Animal Studies ◽  
Human Lung ◽  
Unmet Need ◽  
Three Dimensional ◽  
Lung Cells ◽  
Lung Physiology ◽  
And Function

Differences in lung anatomy between mice and humans, as well as frequently disappointing results when using animal models for drug discovery, emphasise the unmet need for in vitro models that can complement animal studies and improve our understanding of human lung physiology, regeneration and disease. Recent papers have highlighted the use of three-dimensional organoids and organs-on-a-chip to mimic tissue morphogenesis and function in vitro. Here, we focus on the respiratory system and provide an overview of these in vitro models, which can be derived from primary lung cells and pluripotent stem cells, as well as healthy or diseased lungs. We emphasise their potential application in studies of respiratory development, regeneration and disease modelling.

scholarly journals Biomimetic human small muscular pulmonary arteries

2020 ◽  
Vol 6 (13) ◽  
pp. eaaz2598 ◽  
Author(s):  
Qianru Jin ◽  
Anil Bhatta ◽  
Jayson V. Pagaduan ◽  
Xing Chen ◽  
Hoku West-Foyle ◽  
...  
Keyword(s):  
Pulmonary Arteries ◽  
In Vitro Models ◽  
Structure And Function ◽  
Nitric Oxide Production ◽  
New Paradigm ◽  
Public Health Challenge ◽  
Pulmonary Arterial ◽  
Spatial Positioning ◽  
And Function

Changes in structure and function of small muscular arteries play a major role in the pathophysiology of pulmonary hypertension, a burgeoning public health challenge. Improved anatomically mimetic in vitro models of these microvessels are urgently needed because nonhuman vessels and previous models do not accurately recapitulate the microenvironment and architecture of the human microvascular wall. Here, we describe parallel biofabrication of photopatterned self-rolled biomimetic pulmonary arterial microvessels of tunable size and infrastructure. These microvessels feature anatomically accurate layering and patterning of aligned human smooth muscle cells, extracellular matrix, and endothelial cells and exhibit notable increases in endothelial longevity and nitric oxide production. Computational image processing yielded high-resolution 3D perspectives of cells and proteins. Our studies provide a new paradigm for engineering multicellular tissues with precise 3D spatial positioning of multiple constituents in planar moieties, providing a biomimetic platform for investigation of microvascular pathobiology in human disease.

scholarly journals Effects of mesenchymal stromal cell-conditioned media on measures of lung structure and function: a systematic review and meta-analysis of preclinical studies

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Alvaro Moreira ◽  
Rija Naqvi ◽  
Kristen Hall ◽  
Chimobi Emukah ◽  
John Martinez ◽  
...  
Keyword(s):  
Systematic Review ◽  
Animal Models ◽  
Lung Disease ◽  
Mesenchymal Stromal Cell ◽  
Stromal Cell ◽  
Human Lung ◽  
Meta Analysis ◽  
Structure And Function ◽  
Lung Structure ◽  
And Function

Abstract Background Lung disease is a leading cause of morbidity and mortality. A breach in the lung alveolar-epithelial barrier and impairment in lung function are hallmarks of acute and chronic pulmonary illness. This review is part two of our previous work. In part 1, we demonstrated that CdM is as effective as MSCs in modulating inflammation. Herein, we investigated the effects of mesenchymal stromal cell (MSC)-conditioned media (CdM) on (i) lung architecture/function in animal models mimicking human lung disease, and (ii) performed a head-to-head comparison of CdM to MSCs. Methods Adhering to the animal Systematic Review Centre for Laboratory animal Experimentation protocol, we conducted a search of English articles in five medical databases. Two independent investigators collected information regarding lung: alveolarization, vasculogenesis, permeability, histologic injury, compliance, and measures of right ventricular hypertrophy and right pulmonary pressure. Meta-analysis was performed to generate random effect size using standardized mean difference with 95% confidence interval. Results A total of 29 studies met inclusion. Lung diseases included bronchopulmonary dysplasia, asthma, pulmonary hypertension, acute respiratory distress syndrome, chronic obstructive pulmonary disease, and pulmonary fibrosis. CdM improved all measures of lung structure and function. Moreover, no statistical difference was observed in any of the lung measures between MSCs and CdM. Conclusions In this meta-analysis of animal models recapitulating human lung disease, CdM improved lung structure and function and had an effect size comparable to MSCs.

scholarly journals Microengineered human blood–brain barrier platform for understanding nanoparticle transport mechanisms

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Song Ih Ahn ◽  
Yoshitaka J. Sei ◽  
Hyun-Ji Park ◽  
Jinhwan Kim ◽  
Yujung Ryu ◽  
...  
Keyword(s):  
Animal Models ◽  
Blood Brain Barrier ◽  
Neurological Diseases ◽  
Structure And Function ◽  
Brain Barrier ◽  
Cellular Interactions ◽  
Gene Expressions ◽  
Blood Brain ◽  
And Function

AbstractChallenges in drug development of neurological diseases remain mainly ascribed to the blood–brain barrier (BBB). Despite the valuable contribution of animal models to drug discovery, it remains difficult to conduct mechanistic studies on the barrier function and interactions with drugs at molecular and cellular levels. Here we present a microphysiological platform that recapitulates the key structure and function of the human BBB and enables 3D mapping of nanoparticle distributions in the vascular and perivascular regions. We demonstrate on-chip mimicry of the BBB structure and function by cellular interactions, key gene expressions, low permeability, and 3D astrocytic network with reduced reactive gliosis and polarized aquaporin-4 (AQP4) distribution. Moreover, our model precisely captures 3D nanoparticle distributions at cellular levels and demonstrates the distinct cellular uptakes and BBB penetrations through receptor-mediated transcytosis. Our BBB platform may present a complementary in vitro model to animal models for prescreening drug candidates for the treatment of neurological diseases.

Bioengineered in vitro Vascular Models for Applications in Interventional Radiology

2019 ◽  
Vol 24 (45) ◽  
pp. 5367-5374 ◽  
Author(s):  
Xiaoyun Li ◽  
Seyed M. Moosavi-Basri ◽  
Rahul Sheth ◽  
Xiaoying Wang ◽  
Yu S. Zhang
Keyword(s):  
Interventional Radiology ◽  
Animal Models ◽  
Blood Vessels ◽  
In Vitro Models ◽  
The Past ◽  
Endovascular Interventions ◽  
Conventional Animal ◽  
Vascular Structures

The role of endovascular interventions has progressed rapidly over the past several decades. While animal models have long-served as the mainstay for the advancement of this field, the use of in vitro models has become increasingly widely adopted with recent advances in engineering technologies. Here, we review the strategies, mainly including bioprinting and microfabrication, which allow for fabrication of biomimetic vascular models that will potentially serve to supplement the conventional animal models for convenient investigations of endovascular interventions. Besides normal blood vessels, those in diseased states, such as thrombosis, may also be modeled by integrating cues that simulate the microenvironment of vascular disorders. These novel engineering strategies for the development of biomimetic in vitro vascular structures will possibly enable unconventional means of studying complex endovascular intervention problems that are otherwise hard to address using existing models.

scholarly journals Modelling the Human Placental Interface In Vitro—A Review

Micromachines ◽  
2021 ◽  
Vol 12 (8) ◽  
pp. 884
Author(s):  
Marta Cherubini ◽  
Scott Erickson ◽  
Kristina Haase
Keyword(s):  
Drug Testing ◽  
Cell Types ◽  
In Vitro Models ◽  
Placental Development ◽  
Scientific Challenge ◽  
Induced Pluripotent ◽  
And Function ◽  
And Control

Acting as the primary link between mother and fetus, the placenta is involved in regulating nutrient, oxygen, and waste exchange; thus, healthy placental development is crucial for a successful pregnancy. In line with the increasing demands of the fetus, the placenta evolves throughout pregnancy, making it a particularly difficult organ to study. Research into placental development and dysfunction poses a unique scientific challenge due to ethical constraints and the differences in morphology and function that exist between species. Recently, there have been increased efforts towards generating in vitro models of the human placenta. Advancements in the differentiation of human induced pluripotent stem cells (hiPSCs), microfluidics, and bioprinting have each contributed to the development of new models, which can be designed to closely match physiological in vivo conditions. By including relevant placental cell types and control over the microenvironment, these new in vitro models promise to reveal clues to the pathogenesis of placental dysfunction and facilitate drug testing across the maternal–fetal interface. In this minireview, we aim to highlight current in vitro placental models and their applications in the study of disease and discuss future avenues for these in vitro models.

scholarly journals In vitro models of fetal lung development to enhance research into congenital lung diseases

2021 ◽  
Author(s):  
Soichi Shibuya ◽  
Jessica Allen-Hyttinen ◽  
Paolo De Coppi ◽  
Federica Michielin
Keyword(s):  
Lung Development ◽  
Lung Diseases ◽  
Ex Vivo ◽  
Fetal Lung ◽  
Branching Morphogenesis ◽  
In Vitro Models ◽  
Normal Lung ◽  
Novel Therapeutic Strategies ◽  
Pseudoglandular Stage

Abstract Purpose This paper aims to build upon previous work to definitively establish in vitro models of murine pseudoglandular stage lung development. These can be easily translated to human fetal lung samples to allow the investigation of lung development in physiologic and pathologic conditions. Methods Lungs were harvested from mouse embryos at E12.5 and cultured in three different settings, i.e., whole lung culture, mesenchyme-free epithelium culture, and organoid culture. For the whole lung culture, extracted lungs were embedded in Matrigel and incubated on permeable filters. Separately, distal epithelial tips were isolated by firstly removing mesothelial and mesenchymal cells, and then severing the tips from the airway tubes. These were then cultured either in branch-promoting or self-renewing conditions. Results Cultured whole lungs underwent branching morphogenesis similarly to native lungs. Real-time qPCR analysis demonstrated expression of key genes essential for lung bud formation. The culture condition for epithelial tips was optimized by testing different concentrations of FGF10 and CHIR99021 and evaluating branching formation. The epithelial rudiments in self-renewing conditions formed spherical 3D structures with homogeneous Sox9 expression. Conclusion We report efficient protocols for ex vivo culture systems of pseudoglandular stage mouse embryonic lungs. These models can be applied to human samples and could be useful to paediatric surgeons to investigate normal lung development, understand the pathogenesis of congenital lung diseases, and explore novel therapeutic strategies.

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