scholarly journals Xenobiotica-metabolizing enzymes in the lung of experimental animals, man and in human lung models

2019 ◽  
Vol 93 (12) ◽  
pp. 3419-3489 ◽  
Author(s):  
F. Oesch ◽  
E. Fabian ◽  
Robert Landsiedel
Keyword(s):  
Human Lung ◽  
Cytochromes P450 ◽  
Xenobiotic Metabolism ◽  
In Vitro Models ◽  
Work Place ◽  
Individual Species ◽  
Alveolar Type ◽  
Vitro Model ◽  
Few Data

Abstract The xenobiotic metabolism in the lung, an organ of first entry of xenobiotics into the organism, is crucial for inhaled compounds entering this organ intentionally (e.g. drugs) and unintentionally (e.g. work place and environmental compounds). Additionally, local metabolism by enzymes preferentially or exclusively occurring in the lung is important for favorable or toxic effects of xenobiotics entering the organism also by routes other than by inhalation. The data collected in this review show that generally activities of cytochromes P450 are low in the lung of all investigated species and in vitro models. Other oxidoreductases may turn out to be more important, but are largely not investigated. Phase II enzymes are generally much higher with the exception of UGT glucuronosyltransferases which are generally very low. Insofar as data are available the xenobiotic metabolism in the lung of monkeys comes closed to that in the human lung; however, very few data are available for this comparison. Second best rate the mouse and rat lung, followed by the rabbit. Of the human in vitro model primary cells in culture, such as alveolar macrophages and alveolar type II cells as well as the A549 cell line appear quite acceptable. However, (1) this generalization represents a temporary oversimplification born from the lack of more comparable data; (2) the relative suitability of individual species/models is different for different enzymes; (3) when more data become available, the conclusions derived from these comparisons quite possibly may change.

Mesothelial Cells

2007 ◽  
Vol 27 (2_suppl) ◽  
pp. 110-115 ◽  
Author(s):  
Susan Yung ◽  
Chan Tak Mao
Keyword(s):  
Mesothelial Cell ◽  
In Vitro Models ◽  
Mesothelial Cells ◽  
Dynamic Membrane ◽  
Peritoneal Mesothelial Cells ◽  
Immunohistochemical Markers ◽  
Vitro Model ◽  
And Function

♦ Background The introduction of peritoneal dialysis (PD) as a modality of renal replacement therapy has provoked much interest in the biology of the peritoneal mesothelial cell. Mesothelial cells isolated from omental tissue have immunohistochemical markers that are identical to those of mesothelial stem cells, and omental mesothelial cells can be cultivated in vitro to study changes to their biologic functions in the setting of PD. ♦ Method The present article describes the structure and function of mesothelial cells in the normal peritoneum and details the morphologic changes that occur after the introduction of PD. Furthermore, this article reviews the literature of mesothelial cell culture and the limitations of in vitro studies. ♦ Results The mesothelium is now considered to be a dynamic membrane that plays a pivotal role in the homeostasis of the peritoneal cavity, contributing to the control of fluid and solute transport, inflammation, and wound healing. These functional properties of the mesothelium are compromised in the setting of PD. Cultures of peritoneal mesothelial cells from omental tissue provide a relevant in vitro model that allows researchers to assess specific molecular pathways of disease in a distinct population of cells. Structural and functional attributes of mesothelial cells are discussed in relation to long-term culture, proliferation potential, age of tissue donor, use of human or animal in vitro models, and how the foregoing factors may influence in vitro data. ♦ Conclusions The ability to propagate mesothelial cells in culture has resulted, over the past two decades, in an explosion of mesothelial cell research pertaining to PD and peritoneal disorders. Independent researchers have highlighted the potential use of mesothelial cells as targets for gene therapy or transplantation in the search to provide therapeutic strategies for the preservation of the mesothelium during chemical or bacterial injury.

scholarly journals Mesenchymal Stem Cells as a Promising Cell Source for Integration in Novel In Vitro Models

Biomolecules ◽  
2020 ◽  
Vol 10 (9) ◽  
pp. 1306
Author(s):  
Ann-Kristin Afflerbach ◽  
Mark D. Kiri ◽  
Tahir Detinis ◽  
Ben M. Maoz
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Cell Types ◽  
In Vitro Models ◽  
Cell Source ◽  
Fundamental Research ◽  
Multiple Cell ◽  
Vitro Model

The human-relevance of an in vitro model is dependent on two main factors—(i) an appropriate human cell source and (ii) a modeling platform that recapitulates human in vivo conditions. Recent years have brought substantial advancements in both these aspects. In particular, mesenchymal stem cells (MSCs) have emerged as a promising cell source, as these cells can differentiate into multiple cell types, yet do not raise the ethical and practical concerns associated with other types of stem cells. In turn, advanced bioengineered in vitro models such as microfluidics, Organs-on-a-Chip, scaffolds, bioprinting and organoids are bringing researchers ever closer to mimicking complex in vivo environments, thereby overcoming some of the limitations of traditional 2D cell cultures. This review covers each of these advancements separately and discusses how the integration of MSCs into novel in vitro platforms may contribute enormously to clinical and fundamental research.

scholarly journals Organic cation transporter function in different in vitro models of human lung epithelium

2015 ◽  
Vol 80 ◽  
pp. 82-88 ◽  
Author(s):  
Johanna J. Salomon ◽  
Julia C. Gausterer ◽  
Tohru Yahara ◽  
Ken-ichi Hosoya ◽  
Hanno Huwer ◽  
...  
Keyword(s):  
Organic Cation ◽  
Human Lung ◽  
Organic Cation Transporter ◽  
In Vitro Models ◽  
Lung Epithelium

scholarly journals Encapsulated multicellular tumor spheroids as a novel in vitro model to study small size tumors

2003 ◽  
Vol 57 (12) ◽  
pp. 585-588 ◽  
Author(s):  
Elena Markvicheva ◽  
Lina Bezdetnaya ◽  
Artur Bartkowiak ◽  
Annie Marc ◽  
Jean-Louis Gorgen ◽  
...  
Keyword(s):  
Tumor Cells ◽  
Tumor Biology ◽  
Cell Encapsulation ◽  
Large Cell ◽  
In Vitro Models ◽  
Multicellular Tumor Spheroids ◽  
Tumor Spheroids ◽  
Vitro Model

Presently multicellular tumor spheroids (MTS) are being widely used in various aspects of tumor biology, including studies in biology and photodynamic therapy. The cellular organization of spheroids allows the recreation of in vivo small tumors much better than all common two-dimensional in vitro models. The cell encapsulation method could be proposed as a novel technique to quickly and easily prepare a large number of spheroids with narrow size distribution within a desirable diameter range. Moreover, the proposed technique for spheroid generation using encapsulated growing tumor cells could provide entirely new avenues to develop a novel spheroid co-culture model (for instance, the in vitro co-cultvation of tumor cells and monocytes, or epithelial cells, or fibroblasts etc). The current research was aimed at developing a simple and reliable method to encapsulate tumor cells and to cultivate them in vitro. In order to generate spheroids, MCF-7 cells were encapsulated and cultivated in 200 ml T-flasks in a 5% CO2 atmosphere at 37?C for 4-5 weeks. The cell proliferation was easily observed using a light microscope. The cells grew in aggregates increasing in size with time. The cell growth resulted in the formation of large cell clusters (spheroids) which filled the whole microcapsule volume in 4-5 weeks.

Abstract TP492: Novel in vitro Model of Arteriovenous Malformation for Endovascular Embolization and Flow Analysis

Stroke ◽  
2020 ◽  
Vol 51 (Suppl_1) ◽  
Author(s):  
Naoki Kaneko ◽  
Henrik Ullman ◽  
Fadil Ali ◽  
Philipp Berg ◽  
Yinn Cher Ooi ◽  
...  
Keyword(s):  
Arteriovenous Malformation ◽  
In Vitro Model ◽  
Flow Analysis ◽  
Real Life ◽  
In Vitro Models ◽  
Endovascular Embolization ◽  
Experimental Models ◽  
Cfd Analysis ◽  
Vitro Model

Introduction: 3D printed human vascular in vitro models of aneurysms and acute stroke have been utilized for training, simulation and device development. However, there are no realistic in vitro arteriovenous malformation (AVM) models. Current experimental models analyzing the efficacy of embolic materials or flow conditions are limited by their simplistic design, lacking complex AVM nidus anatomic features. The purpose of this study is to develop a new in vitro AVM model for embolic material testing and flow analysis. Methods: 3D images of the AVM nidus were extracted from 3D rotational angiography from a patient. Artificial feeders and drainers were added to the nidus and an inner vascular mold was printed using a 3D printer. The inner mold was coated with polydimethylsiloxanes. The inner plastic mold was removed by acetone, leaving a hollow AVM model. ONYX injection and 4DFlow MRI (Phase Contrast MRA) were performed using the AVM models. In addition, computational fluid dynamics (CFD) analysis was performed to compare flow rate with 4DFlow MRI. Results: An in vitro AVM model with realistic representation of nidus vasculature and complexity was successfully created. Liquid onyx injection performed in the in vitro model successfully replicated real-life treatment conditions. The model effectively simulated plug and push technique before penetration of the ONYX into the AVM nidus. 4DFlow MRI flow rates were similar to the CFD analysis. Conclusions: An in vitro AVM model using 3D printing technology was successfully created. The model demonstrated realistic pliability during ONYX injection. This in vitro AVM model may represent a useful tool for training and development of new materials, and have potential of highly-resolved flow quantifications.

scholarly journals Beneficial Effect of Tempol, a Membrane-Permeable Radical Scavenger, on Inflammation and Osteoarthritis in In Vitro Models

Biomolecules ◽  
2021 ◽  
Vol 11 (3) ◽  
pp. 352
Author(s):  
Giovanna Calabrese ◽  
Alessio Ardizzone ◽  
Michela Campolo ◽  
Sabrina Conoci ◽  
Emanuela Esposito ◽  
...  
Keyword(s):  
Biological Properties ◽  
In Vitro Models ◽  
Radical Scavenger ◽  
Proinflammatory Mediators ◽  
Nitrite Production ◽  
Inflammatory State ◽  
Anti Inflammatory ◽  
Vitro Model ◽  
Antioxidant Effects

Osteoarthritis (OA) is one of the most common and widespread diseases which is highly disabling for humans. This makes OA a chronic disease for which it is urgent to find new therapeutic strategies. The inflammatory state in OA contributes to its progression through multiple mechanisms involving the recruitment of phagocytes and leukocytes, inflammatory response, and reactive oxygen species (ROS) production. Tempol (4-hydroxy-2,2,6,6-tetramethylpiperidine-1-oxyl) is classifiable as a piperidine nitroxide, with excellent antioxidant effects, while its anti-inflammatory role is not yet clear. On this basis, we explored its promising biological properties in two in vitro model:, macrophage (J774) and chondrocyte (CC) cell lines. With this aim in mind, we induced inflammation in J774 and CC using lipopolysaccharide (LPS) and Interleukin1β (IL-1β), and after 24, 72 and 168 h of tempol treatment analyzed their effects on cytotoxicity and anti-inflammatory activity. Our data suggested that tempol treatment is able to reduce inflammation and nitrite production in LPS-induced J774 as well as reducing the production of proinflammatory mediators including cytokines, enzymes, and metalloproteases (MMPs) in IL-1β-stimulated CC. Thus, since inflammation and oxidative stress have a crucial role in the pathogenesis and progression of OA, tempol could be considered as a new therapeutic approach for this pathology.

The Use of Human Lung Slices in Toxicology

1994 ◽  
Vol 13 (7) ◽  
pp. 466-471 ◽  
Author(s):  
Robyn L. Fisher ◽  
Mary S. Smith ◽  
Steven J. Hasal ◽  
Katherine S. Hasal ◽  
A. Jay Gandolfi ◽  
...  
Keyword(s):  
Protein Synthesis ◽  
Human Lung ◽  
Balloon Catheter ◽  
Human Lung Tissue ◽  
Tissue Mass ◽  
Dependent Inhibition ◽  
Dose Dependent Inhibition ◽  
Vitro Model ◽  
Dose Dependent

1 Successful use of agar-filled precision-cut rat lung slices in dynamic organ culture prompted the use of this technology with human lung. 2 The larger tissue mass of a human lung required that the trachea be cannulated with a balloon catheter and subsequently inflated with 4 liters of warm agar/medium mixture and then cooled before being precision-cut into 500 μm thick slices. 3 To characterize the human lung slices, viability and the effects of acrolein and nitrofurantoin were assessed over a period of 24 h using protein synthesis and nonprotein sulfhydryl content. 4 Control human lung slices synthesized protein at a linear rate and maintained a stable nonprotein sulfhydryl content for 24 h. 5 Slices incubated with acrolein exhibited no significant decrease in protein synthesis or nonprotein sulfhydryl levels until 24 h. 6 Incubation with nitrofurantoin exhibited a definite time- and dose-dependent inhibition of protein synthesis, and depletion of the cellular thiol pool. 7 These results indicate that this human lung tissue slice system may be used as an in vitro model to identify and screen pneumotoxicants.

scholarly journals Patient-derived organoids (PDOs) as a novel in vitro model for neuroblastoma tumours

BMC Cancer ◽  
2019 ◽  
Vol 19 (1) ◽  
Author(s):  
P. Fusco ◽  
B. Parisatto ◽  
E. Rampazzo ◽  
L. Persano ◽  
C. Frasson ◽  
...  
Keyword(s):  
Cell Adhesion ◽  
Therapy Response ◽  
In Vitro Models ◽  
Neural Cell ◽  
Cellular Heterogeneity ◽  
Patient Specific ◽  
Preclinical Model ◽  
Neural Cell Adhesion ◽  
Vitro Model

Abstract Background Neuroblastoma (NB) is a paediatric tumour of the sympathetic nervous system. Half of all cases are defined high-risk with an overall survival less than 40% at 5 years from diagnosis. The lack of in vitro models able to recapitulate the intrinsic heterogeneity of primary NB tumours has hindered progress in understanding disease pathogenesis and therapy response. Methods Here we describe the establishment of 6 patient-derived organoids (PDOs) from cells of NB tumour biopsies capable of self-organising in a structure resembling the tissue of origin. Results PDOs recapitulate the histological architecture typical of the NB tumour. Moreover, PDOs expressed NB specific markers such as neural cell adhesion molecules, NB84 antigen, synaptophysin (SYP), chromogranin A (CHGA) and neural cell adhesion molecule NCAM (CD56). Analyses of whole genome genotyping array revealed that PDOs maintained patient-specific chromosomal aberrations such as MYCN amplification, deletion of 1p and gain of chromosome 17q. Furthermore, the PDOs showed stemness features and retained cellular heterogeneity reflecting the high heterogeneity of NB tumours. Conclusions We were able to create a novel preclinical model for NB exhibiting self-renewal property and allowing to obtain a reservoir of NB patients’ biological material useful for the study of NB molecular pathogenesis and to test drugs for personalised treatments.

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