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 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.

scholarly journals A three-dimensional model of human lung development and disease from pluripotent stem cells

2017 ◽  
Vol 19 (5) ◽  
pp. 542-549 ◽  
Author(s):  
Ya-Wen Chen ◽  
Sarah Xuelian Huang ◽  
Ana Luisa Rodrigues Toste de Carvalho ◽  
Siu-Hong Ho ◽  
Mohammad Naimul Islam ◽  
...  
Keyword(s):  
Stem Cells ◽  
Pluripotent Stem Cells ◽  
Lung Development ◽  
Human Lung ◽  
Three Dimensional ◽  
Dimensional Model ◽  
Three Dimensional Model

scholarly journals Spheres of Influence: Insights into Salmonella Pathogenesis from Intestinal Organoids

2020 ◽  
Vol 8 (4) ◽  
pp. 504 ◽  
Author(s):  
Smriti Verma ◽  
Stefania Senger ◽  
Bobby J. Cherayil ◽  
Christina S. Faherty
Keyword(s):  
Animal Studies ◽  
Three Dimensional ◽  
Cell Types ◽  
Experimental Models ◽  
Primary Cells ◽  
Spheres Of Influence ◽  
Transformed Cell Lines ◽  
And Function

The molecular complexity of host-pathogen interactions remains poorly understood in many infectious diseases, particularly in humans due to the limited availability of reliable and specific experimental models. To bridge the gap between classical two-dimensional culture systems, which often involve transformed cell lines that may not have all the physiologic properties of primary cells, and in vivo animal studies, researchers have developed the organoid model system. Organoids are complex three-dimensional structures that are generated in vitro from primary cells and can recapitulate key in vivo properties of an organ such as structural organization, multicellularity, and function. In this review, we discuss how organoids have been deployed in exploring Salmonella infection in mice and humans. In addition, we summarize the recent advancements that hold promise to elevate our understanding of the interactions and crosstalk between multiple cell types and the microbiota with Salmonella. These models have the potential for improving clinical outcomes and future prophylactic and therapeutic intervention strategies.

scholarly journals Polyphosphate Reverses the Toxicity of the Quasi-Enzyme Bleomycin on Alveolar Endothelial Lung Cells In Vitro

Cancers ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 750
Author(s):  
Werner E. G. Müller ◽  
Meik Neufurth ◽  
Shunfeng Wang ◽  
Heinz C. Schröder ◽  
Xiaohong Wang
Keyword(s):  
Dna Damage ◽  
Human Lung ◽  
Dna Integrity ◽  
Lung Cells ◽  
Antitumor Antibiotic ◽  
Cell Toxicity ◽  
Inorganic Polyphosphate ◽  
Human Lung Cells ◽  
Anti Cancer

The anti-cancer antitumor antibiotic bleomycin(s) (BLM) induces athyminic sites in DNA after its activation, a process that results in strand splitting. Here, using A549 human lung cells or BEAS-2B cells lunc cells, we show that the cell toxicity of BLM can be suppressed by addition of inorganic polyphosphate (polyP), a physiological polymer that accumulates and is released from platelets. BLM at a concentration of 20 µg ml−1 causes a decrease in cell viability (by ~70%), accompanied by an increased DNA damage and chromatin expansion (by amazingly 6-fold). Importantly, the BLM-caused effects on cell growth and DNA integrity are substantially suppressed by polyP. In parallel, the enlargement of the nuclei/chromatin in BLM-treated cells (diameter, 20–25 µm) is normalized to ~12 µm after co-incubation of the cells with BLM and polyP. A sequential application of the drugs (BLM for 3 days, followed by an exposure to polyP) does not cause this normalization. During co-incubation of BLM with polyP the gene for the BLM hydrolase is upregulated. It is concluded that by upregulating this enzyme polyP prevents the toxic side effects of BLM. These data might also contribute to an application of BLM in COVID-19 patients, since polyP inhibits binding of SARS-CoV-2 to cellular ACE2.

scholarly journals Induction of functional hypothalamus and pituitary tissues from pluripotent stem cells for regenerative medicine

2020 ◽  
Author(s):  
Mayuko Kano ◽  
Hidetaka Suga ◽  
Hiroshi Arima
Keyword(s):  
Stem Cells ◽  
Regenerative Medicine ◽  
Pluripotent Stem Cells ◽  
Hormone Replacement ◽  
Three Dimensional ◽  
Embryonic Stem ◽  
Hormone Deficiency ◽  
Adrenal Crisis ◽  
Mouse Escs

Abstract The hypothalamus and pituitary have been identified to play essential roles in maintaining homeostasis. Various diseases can disrupt the functions of these systems, which can often result in serious lifelong symptoms. The current treatment for hypopituitarism involves hormone replacement therapy. However, exogenous drug administration cannot mimic the physiological changes that are a result of hormone requirements. Therefore, patients are at a high risk of severe hormone deficiency, including adrenal crisis. Pluripotent stem cells (PSCs) self-proliferate and differentiate into all types of cells. The generation of endocrine tissues from PSCs has been considered as another new treatment for hypopituitarism. Our colleagues established a three-dimensional culture method for embryonic stem cells (ESCs). In this culture, the ESC-derived aggregates exhibit self-organization and spontaneous formation of highly ordered patterning. Recent results have shown that strict removal of exogenous patterning factors during early differentiation efficiently induces rostral hypothalamic progenitors from mouse ESCs. These hypothalamic progenitors generate vasopressinergic neurons, which release neuropeptides upon exogenous stimulation. Subsequently, we reported adenohypophysis tissue self-formation in three-dimensional cultures of mouse ESCs. The ESCs were found to differentiate into both non-neural oral ectoderm and hypothalamic neuroectoderm in adjacent layers. Interactions between the two tissues appear to be critically important for in vitro induction of a Rathke's pouch-like developing embryo. Various endocrine cells were differentiated from non-neural ectoderm. The induced corticotrophs efficiently secreted adrenocorticotropic hormone when engrafted in vivo, which rescued hypopituitary hosts. For future regenerative medicine, generation of hypothalamic and pituitary tissues from human PSCs is necessary. We and other groups succeeded in establishing a differentiation method with the use of human PSCs. Researchers could use these methods for models of human diseases to elucidate disease pathology or screen potential therapeutics.

scholarly journals Platelet-Rich Plasma: New Performance Understandings and Therapeutic Considerations in 2020

2020 ◽  
Author(s):  
Peter Everts ◽  
Kentaro Onishi ◽  
Prathap Jayaram ◽  
José Fábio Lana ◽  
and Kenneth Mautner
Keyword(s):  
Tissue Repair ◽  
Animal Studies ◽  
Platelet Rich Plasma ◽  
Unmet Need ◽  
Treatment Protocols ◽  
Rehabilitation Protocols ◽  
Recent Developments ◽  
Treatment Plans ◽  
New Research

Emerging autologous cellular therapies that utilize platelet-rich plasma (PRP) applications have the potential to play adjunctive roles in a variety of regenerative medicine treatment plans. There is a global unmet need for tissue repair strategies to treat musculoskeletal (MSK) and spinal disorders, osteoarthritis (OA), and patients with chronic complex and recalcitrant wounds. PRP therapy is based on the fact that platelet growth factors (PGFs) support the three phases of wound healing and repair cascade (inflammation, proliferation, remodeling). Many different PRP formulations have been evaluated, originating from human, in vitro, and animal studies. However, recommendations from in vitro and animal research often lead to different clinical outcomes because it is difficult to translate non-clinical study outcomes and methodology recommendations to human clinical treatment protocols. In recent years, progress has been made in understanding PRP technology and the concepts for bioformulation, and new research directives and new indications have been suggested. In this review, we will discuss recent developments regarding PRP preparation and composition regarding platelet dosing, leukocyte activities concerning innate and adaptive immunomodulation, serotonin (5-HT) effects and pain killing. Furthermore, we discuss PRP mechanisms related to inflammation and angiogenesis in tissue repair and regenerative processes. Lastly, we will review the effect of certain drugs on PRP activity, and the combination of PRP and rehabilitation protocols.

Pathobiological Effects of Fibers and Tobacco-Related Chemicals in Human Lung Cells In Vitro

1989 ◽  
pp. 103-117
Author(s):  
C. C. Harris ◽  
J. C. Willey ◽  
N. Matsukura ◽  
J. F. Lechner ◽  
M. Miyashita ◽  
...  
Keyword(s):  
Human Lung ◽  
Lung Cells ◽  
Human Lung Cells

Advances in aptamer evolution and engineering

2016 ◽  
Author(s):  
◽  
Khalid Kamal Alam
Keyword(s):  
High Throughput Sequencing ◽  
Target Selection ◽  
Three Dimensional ◽  
Rna Aptamers ◽  
Hiv Reverse Transcriptase ◽  
University Of Missouri ◽  
Selection Approach ◽  
And Function ◽  
The University

[ACCESS RESTRICTED TO THE UNIVERSITY OF MISSOURI AT AUTHOR'S REQUEST.] Aptamers are single-stranded nucleic acids that fold into unique three-dimensional shapes that allow them to bind with high affinity and specificity to targets of interest. They are selected through the process of in vitro evolution, wherein large libraries of randomized sequence are iteratively partitioned and amplified to enrich for high-fitness, functional molecules. Selected libraries are sequenced and individual aptamers are characterized for their structure and function. Aptamers have found use as research tools, diagnostics, and therapeutics and in the control of biological systems. The work described herein presents several advancements to the selection and application of aptamers. I first describe an aptamer bioinformatics platform, FASTAptamer, which performs the primary sequence tasks common to all combinatorial selection techniques. I then describe a poly-target selection approach that leverages high-throughput sequencing, the aptamer bioinformatics platform, and parallel selections against a family of related targets to identify the first RNA aptamers capable of potent broad-spectrum inhibition of HIV reverse transcriptase. Finally, this work describes the engineering and in vitro validation of a bifurcated aptamer, Split-Broccoli, for direct visualization of RNA:RNA processes.

scholarly journals Renal reabsorption in 3D vascularized proximal tubule models

2019 ◽  
Vol 116 (12) ◽  
pp. 5399-5404 ◽  
Author(s):  
Neil Y. C. Lin ◽  
Kimberly A. Homan ◽  
Sanlin S. Robinson ◽  
David B. Kolesky ◽  
Nathan Duarte ◽  
...  
Keyword(s):  
Proximal Tubule ◽  
Disease Modeling ◽  
Three Dimensional ◽  
Kidney Tissue ◽  
Renal Reabsorption ◽  
Native Kidney ◽  
Glucose Reabsorption ◽  
Diseased State ◽  
And Function

Three-dimensional renal tissues that emulate the cellular composition, geometry, and function of native kidney tissue would enable fundamental studies of filtration and reabsorption. Here, we have created 3D vascularized proximal tubule models composed of adjacent conduits that are lined with confluent epithelium and endothelium, embedded in a permeable ECM, and independently addressed using a closed-loop perfusion system to investigate renal reabsorption. Our 3D kidney tissue allows for coculture of proximal tubule epithelium and vascular endothelium that exhibits active reabsorption via tubular–vascular exchange of solutes akin to native kidney tissue. Using this model, both albumin uptake and glucose reabsorption are quantified as a function of time. Epithelium–endothelium cross-talk is further studied by exposing proximal tubule cells to hyperglycemic conditions and monitoring endothelial cell dysfunction. This diseased state can be rescued by administering a glucose transport inhibitor. Our 3D kidney tissue provides a platform for in vitro studies of kidney function, disease modeling, and pharmacology.

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