scholarly journals A Multi-Modal Toolkit for Studying Neutrophils in Cancer and Beyond

Cancers ◽  
2021 ◽  
Vol 13 (21) ◽  
pp. 5331
Author(s):  
Diana Changirwa ◽  
Jared Schlechte ◽  
Braedon McDonald
Keyword(s):  
Single Cell Analysis ◽  
Ex Vivo ◽  
Neutrophil Function ◽  
Model Systems ◽  
Cellular Heterogeneity ◽  
High Dimensional ◽  
Integrated Analysis ◽  
Functional Plasticity ◽  
Ex Vivo Model

As key effector cells of the innate immune response, neutrophils are rapidly deployed to sites of inflammation where they deliver a payload of potent effector mechanisms that are essential for host defense against pathogens as well as tissue homeostasis. In addition, neutrophils are central contributors to the pathogenesis of a vast spectrum of inflammatory, degenerative, and neoplastic diseases. As our understanding of neutrophils in health and disease continually expands, so too does our appreciation of their complex and dynamic nature in vivo; from development, maturation, and trafficking to cellular heterogeneity and functional plasticity. Therefore, contemporary neutrophil research relies on multiple complementary methodologies to perform integrated analysis of neutrophil phenotypic heterogeneity, organ- and stimulus-specific trafficking mechanisms, as well as tailored effector functions in vivo. This review discusses established and emerging technologies used to study neutrophils, with a focus on in vivo imaging in animal models, as well as next-generation ex vivo model systems to study mechanisms of neutrophil function. Furthermore, we discuss how high-dimensional single-cell analysis technologies are driving a renaissance in neutrophil biology by redefining our understanding of neutrophil development, heterogeneity, and functional plasticity. Finally, we discuss innovative applications and emerging opportunities to integrate these high-dimensional, multi-modal techniques to deepen our understanding of neutrophils in cancer research and beyond.

scholarly journals Considerations to Model Heart Disease in Women with Preeclampsia and Cardiovascular Disease

Cells ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 899
Author(s):  
Clara Liu Chung Ming ◽  
Kimberly Sesperez ◽  
Eitan Ben-Sefer ◽  
David Arpon ◽  
Kristine McGrath ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Cardiovascular Disease ◽  
Ex Vivo ◽  
Myocardial Damage ◽  
Cardiovascular Disorder ◽  
Model Systems ◽  
Ex Vivo Model ◽  
Disease Manifestation

Preeclampsia is a multifactorial cardiovascular disorder diagnosed after 20 weeks of gestation, and is the leading cause of death for both mothers and babies in pregnancy. The pathophysiology remains poorly understood due to the variability and unpredictability of disease manifestation when studied in animal models. After preeclampsia, both mothers and offspring have a higher risk of cardiovascular disease (CVD), including myocardial infarction or heart attack and heart failure (HF). Myocardial infarction is an acute myocardial damage that can be treated through reperfusion; however, this therapeutic approach leads to ischemic/reperfusion injury (IRI), often leading to HF. In this review, we compared the current in vivo, in vitro and ex vivo model systems used to study preeclampsia, IRI and HF. Future studies aiming at evaluating CVD in preeclampsia patients could benefit from novel models that better mimic the complex scenario described in this article.

scholarly journals Considerations to Model Heart Disease in Women with Preeclampsia and Cardiovascular Disease

2021 ◽  
Author(s):  
Clara Liu Chung Ming ◽  
Kimberly Sesperez ◽  
Eitan Ben-Sefer ◽  
David Arpon ◽  
Kristine McGrath ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Cardiovascular Disease ◽  
Ex Vivo ◽  
Myocardial Damage ◽  
Cardiovascular Disorder ◽  
Model Systems ◽  
Ex Vivo Model ◽  
Disease Manifestation

Preeclampsia is a multifactorial cardiovascular disorder diagnosed after 20 weeks of gestation that is the leading cause of death for both mothers and babies in pregnancy. The pathophysiology remains poorly understood due to variability and unpredictability of disease manifestation when studied in animal models. After preeclampsia, both mothers and offspring have a higher risk of cardiovascular disease (CVD) including myocardial infarction or heart attack and heart failure (HF). Myocardial infarction is an acute myocardial damage that can be treated through reperfusion, however, that therapeutic approach leads to ischemic/reperfusion injury (IRI) often leading to HF. In this review, we compared the current in vivo, in vitro and ex vivo model systems used to study preeclampsia, IRI and HF. Future studies aiming at evaluating CVD in preeclampsia patients could benefit from novel models that better mimic the complex scenario described in this article.

scholarly journals Carboplatin response in preclinical models for ovarian cancer: comparison of 2D monolayers, spheroids, ex vivo tumors and in vivo models

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Melica Nourmoussavi Brodeur ◽  
Kayla Simeone ◽  
Kim Leclerc-Deslauniers ◽  
Hubert Fleury ◽  
Euridice Carmona ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cell Lines ◽  
Therapeutic Response ◽  
Ex Vivo ◽  
Model Systems ◽  
Preclinical Models ◽  
Ex Vivo Model ◽  
In Vivo Models ◽  
3D Spheroids

AbstractEpithelial ovarian cancer (EOC) is the most lethal gynecological cancer. Among the key challenges in developing effective therapeutics is the poor translation of preclinical models used in the drug discovery pipeline. This leaves drug attrition rates and costs at an unacceptably high level. Previous work has highlighted the discrepancies in therapeutic response between current in vitro and in vivo models. To address this, we conducted a comparison study to differentiate the carboplatin chemotherapy response across four different model systems including 2D monolayers, 3D spheroids, 3D ex vivo tumors and mouse xenograft models. We used six previously characterized EOC cell lines of varying chemosensitivity and performed viability assays for each model. In vivo results from the mouse model correlated with 2D response in 3/6 cell lines while they correlated with 3D spheroids and the ex vivo model in 4/6 and 5/5 cell lines, respectively. Our results emphasize the variability in therapeutic response across models and demonstrate that the carboplatin response in EOC cell lines cultured in a 3D ex vivo model correlates best with the in vivo response. These results highlight a more feasible, reliable, and cost-effective preclinical model with the highest translational potential for drug screening and prediction studies in EOC.

Expression of β-defensin-4 in “an in vivo and ex vivo model” of human osteoarthritic knee meniscus

2011 ◽  
Vol 20 (2) ◽  
pp. 216-222 ◽  
Author(s):  
Giuseppe Musumeci ◽  
Maria Luisa Carnazza ◽  
Rosalia Leonardi ◽  
Carla Loreto
Keyword(s):  
Ex Vivo ◽  
Ex Vivo Model ◽  
Osteoarthritic Knee ◽  
Knee Meniscus

scholarly journals Experimental Models to Study COVID-19 Effect in Stem Cells

Cells ◽  
2021 ◽  
Vol 10 (1) ◽  
pp. 91
Author(s):  
Rishi Man Chugh ◽  
Payel Bhanja ◽  
Andrew Norris ◽  
Subhrajit Saha
Keyword(s):  
Stem Cells ◽  
Ex Vivo ◽  
Drug Efficacy ◽  
Cell Loss ◽  
Experimental Models ◽  
Model Systems ◽  
Virus Infectivity ◽  
Ex Vivo Model ◽  
Global Pandemic ◽  
The Impact

The new strain of coronavirus (severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2)) emerged in 2019 and hence is often referred to as coronavirus disease 2019 (COVID-19). This disease causes hypoxic respiratory failure and acute respiratory distress syndrome (ARDS), and is considered as the cause of a global pandemic. Very limited reports in addition to ex vivo model systems are available to understand the mechanism of action of this virus, which can be used for testing of any drug efficacy against virus infectivity. COVID-19 induces tissue stem cell loss, resulting inhibition of epithelial repair followed by inflammatory fibrotic consequences. Development of clinically relevant models is important to examine the impact of the COVID-19 virus in tissue stem cells among different organs. In this review, we discuss ex vivo experimental models available to study the effect of COVID-19 on tissue stem cells.

scholarly journals Neuraminidase inhibitors rewire neutrophil function in vivo in murine sepsis and ex vivo in COVID-19

2020 ◽  
Author(s):  
Rodrigo O. Formiga ◽  
Flávia C. Amaral ◽  
Camila F. Souza ◽  
Daniel A. G. B. Mendes ◽  
Carlos W. S. Wanderley ◽  
...  
Keyword(s):  
Sialic Acid ◽  
Ex Vivo ◽  
Neutrophil Function ◽  
Human Neutrophils ◽  
Data Sets ◽  
Neuraminidase Inhibitors ◽  
Severe Infections ◽  
Whole Blood Cells ◽  
Neutrophil Dysfunction

ABSTRACTNeutrophil overstimulation plays a crucial role in tissue damage during severe infections. Neuraminidase (NEU)-mediated cleavage of surface sialic acid has been demonstrated to regulate leukocyte responses. Here, we report that antiviral NEU inhibitors constrain host NEU activity, surface sialic acid release, ROS production, and NETs released by microbial-activated human neutrophils. In vivo, treatment with Oseltamivir results in infection control and host survival in peritonitis and pneumonia models of sepsis. Single-cell RNA sequencing re-analysis of publicly data sets of respiratory tract samples from critical COVID-19 patients revealed an overexpression of NEU1 in infiltrated neutrophils. Moreover, Oseltamivir or Zanamivir treatment of whole blood cells from severe COVID-19 patients reduces host NEU-mediated shedding of cell surface sialic acid and neutrophil overactivation. These findings suggest that neuraminidase inhibitors can serve as host-directed interventions to dampen neutrophil dysfunction in severe infections.

scholarly journals The MEMIC: An ex vivo system to model the complexity of the tumor microenvironment

2021 ◽  
Author(s):  
Libuše Janská ◽  
Libi Anandi ◽  
Nell C. Kirchberger ◽  
Zoran S. Marinkovic ◽  
Logan T. Schachtner ◽  
...  
Keyword(s):  
Tumor Microenvironment ◽  
Tumor Cells ◽  
Ex Vivo ◽  
Tumor Stroma ◽  
Stem Cell Differentiation ◽  
Blood Stream ◽  
Direct Access ◽  
Ex Vivo Model

There is an urgent need for accurate, scalable, and cost-efficient experimental systems to model the complexity of the tumor microenvironment. Here, we detail how to fabricate and use the Metabolic Microenvironment Chamber (MEMIC) – a 3D-printed ex vivo model of intratumoral heterogeneity. A major driver of the cellular and molecular diversity in tumors is the accessibility to the blood stream that provides key resources such as oxygen and nutrients. While some tumor cells have direct access to these resources, many others must survive under progressively more ischemic environments as they reside further from the vasculature. The MEMIC is designed to simulate the differential access to nutrients and allows co-culturing different cell types, such as tumor and immune cells. This system is optimized for live imaging and other microscopy-based approaches, and it is a powerful tool to study tumor features such as the effect of nutrient scarcity on tumor-stroma interactions. Due to its adaptable design and full experimental control, the MEMIC provide insights into the tumor microenvironment that would be difficult to obtain via other methods. As a proof of principle, we show that cells sense gradual changes in metabolite concentration resulting in multicellular spatial patterns of signal activation and cell proliferation. To illustrate the ease of studying cell-cell interactions in the MEMIC, we show that ischemic macrophages reduce epithelial features in neighboring tumor cells. We propose the MEMIC as a complement to standard in vitro and in vivo experiments, diversifying the tools available to accurately model, perturb, and monitor the tumor microenvironment, as well as to understand how extracellular metabolites affect other processes such as wound healing and stem cell differentiation.

Alterations of nitric oxide synthase expression and activity during rat lung transplantation

2000 ◽  
Vol 278 (5) ◽  
pp. L1071-L1081 ◽  
Author(s):  
Mingyao Liu ◽  
Lorraine Tremblay ◽  
Stephen D. Cassivi ◽  
Xiao-Hui Bai ◽  
Eric Mourgeon ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Lung Transplantation ◽  
Ex Vivo ◽  
Total Activity ◽  
No Production ◽  
Ex Vivo Model ◽  
Gene And Protein Expression ◽  
Lung Transplants ◽  
Inducible Nos

Decreased nitric oxide (NO) production has been reported during lung transplantation in patients. To study the effects of ischemia and reperfusion on endogenous NO synthase (NOS) expression, both an ex vivo and an in vivo lung injury model for transplantation were used. Donor rat lungs were flushed with cold low-potassium dextran solution and subjected to either cold (4°C for 12 h) or warm (21°C for 4 h) ischemic preservation followed by reperfusion with an ex vivo model. A significant increase in inducible NOS and a decrease in endothelial NOS mRNA was found after reperfusion. These results were confirmed in a rat single-lung transplant model after warm preservation. Interestingly, protein contents of both inducible NOS and endothelial NOS increased in the transplanted lung after 2 h of reperfusion. However, the total activity of NOS in the transplanted lungs remained at very low levels. We conclude that ischemic lung preservation and reperfusion result in altered NOS gene and protein expression with inhibited NOS activity, which may contribute to the injury of lung transplants.

Measurement of bone surface strains on the sheep metacarpus in vivo and ex vivo

2003 ◽  
Vol 16 (01) ◽  
pp. 38-43 ◽  
Author(s):  
R. Steck ◽  
C. Gatzka ◽  
E. Schneider ◽  
P. Niederer ◽  
M. L. Tate
Keyword(s):  
Ex Vivo ◽  
Longitudinal Axis ◽  
Peak Strain ◽  
Bone Surface ◽  
Interstitial Fluid Flow ◽  
Ex Vivo Model ◽  
Physiological Strain ◽  
Bending Load ◽  
Walking Speeds

SummaryBone surface strains were measured on the dorsal ovine metacarpus during normal locomotion on a treadmill at different walking speeds to determine physiological strain levels. These measured strains were related to the strains measured in an ex vivo model of the sheep forelimb with two types of load application: loading by two Schanz-screws and loading via the radius. In vivo, the average surface strains were found to be dependent upon body weight as well as the walking speed. The orientation of the peak principal strain corresponded to the longitudinal axis of the bone. Ex vivo, loads applied via Schanz screws in the screw-loading model lead to strains on the dorsal metacarpus that corresponds to strains experienced in vivo during intermittent peak loads. Screw loading imparted primarily a bending load to the metacarpus, with the dorsal aspect in compression and the palmar aspect in tension. Loads, applied via the radius and the hoof in the radius-loading model, resulted in bone surface strains comparable to those measured during slow walking in vivo. In both ex vivo loading situations, peak strain orientation was parallel to the longitudinal axis of the sheep metacarpus. In conclusion, the results show that although the ex vivo loading models do not exactly replicate the load experienced in vivo, the magnitude and orientation of the principal strains on the dorsal metacarpus are within the range of strains occurring during normal physiological loading. These data validate the physiological significance of the ex vivo model and aid in understanding effects of mechanical loading on interstitial fluid flow and mass transport through bone.

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