scholarly journals An Effective Multi-Stage Liposomal DNA Origami Nanosystem for In Vivo Cancer Therapy

Cancers ◽  
2019 ◽  
Vol 11 (12) ◽  
pp. 1997 ◽  
Author(s):  
Stefano Palazzolo ◽  
Mohamad Hadla ◽  
Concetta Russo Spena ◽  
Isabella Caligiuri ◽  
Rossella Rotondo ◽  
...  
Keyword(s):  
Immune System ◽  
Ex Vivo ◽  
Three Dimensional ◽  
Dna Origami ◽  
Bone Marrow Toxicity ◽  
Ex Vivo Model ◽  
Innovative Drug ◽  
Multi Stage ◽  
Liver Organoids

DNA origami systems could be important candidates for clinical applications. Unfortunately, their intrinsic properties such as the activation of non-specific immune system responses leading to inflammation, instability in physiological solutions, and a short in vivo lifetime are the major challenges for real world applications. A compact short tube DNA origami (STDO) of 30 nm in length and 10 nm in width was designed to fit inside the core of a stealth liposome (LSTDO) of about 150 nm to remote load doxorubicin. Biocompatibility was tested in three-dimensional (3D) organoid cultures and in vivo. Efficacy was evaluated in different cell lines and in a xenograft breast cancer mouse model. As described in a previous work, LSTDO is highly stable and biocompatible, escaping the recognition of the immune system. Here we show that LSTDO have an increased toleration in mouse liver organoids used as an ex vivo model that recapitulate the tissue of origin. This innovative drug delivery system (DDS) improves the antitumoral efficacy and biodistribution of doxorubicin in tumor-bearing mice and decreases bone marrow toxicity. Our application is an attractive system for the remote loading of other drugs able to interact with DNA for the preparation of liposomal formulations.

A Preliminary Model of the Wrist Midcarpal Joint

2021 ◽  
Author(s):  
Martin Pendola ◽  
Catherine Petchprapa ◽  
Ronit Wollstein
Keyword(s):  
Ex Vivo ◽  
Three Dimensional ◽  
Ct Scans ◽  
Ex Vivo Model ◽  
Carpometacarpal Joints ◽  
Force Transfer ◽  
Midcarpal Joint

Abstract Background A challenge to deciphering the effect of structure on function in the wrist involves difficulty in obtaining in-vivo information. To provide a platform to study wrist mechanics using in vivo acquired forces, we developed a model of the midcarpal joint based on computed tomography (CT) scans of normal wrists. Finite element analysis (FEA) can enable application of in vivo collected information to an ex vivo model. Objectives The objectives of this study are to (1) create a three-dimensional model of the midcarpal joint of the wrist based on CT scans and (2) generate separate models for the midcarpal joint based on two distinct wrist types and perform a pilot loading of the model. Methods CT scans from a normal patient database were converted to three-dimensional standard template library (STL) files using OsiriX software. Five type 1 and five type 2 wrists were used for modeling. A simulated load was applied to the carpometacarpal joints in a distal-to-proximal direction, and FEA was used to predict force transfer in the wrist. Results There were 33% type 1 and 67% type 2 wrists. The midcarpal joint dimensional measurements estimated from the model had intermediate agreement between wrist type as measured on CT scan and as predicted by the model: 56% Cohen's kappa (95% confidence interval) = 0.221 (0.05–0.5). Surface stress on the carpometacarpal joints is different in type 1 and type 2 wrists. On loading the neutral wrist, the capitolunate angle was 90 degrees in type 1 wrists and 107 degrees in type 2 wrists (p < 0.0001). Conclusions The model predicted differences in movement and force transfer through the midcarpal joint dependent on structural type. This knowledge can improve our understanding of the development of disparate patterns of degeneration in the wrist.

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 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 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.

scholarly journals Thymosin alpha 1 mitigates cytokine storm in blood cells from COVID-19 patients

2020 ◽  
Author(s):  
Claudia Matteucci ◽  
Antonella Minutolo ◽  
Emanuela Balestrieri ◽  
Vita Petrone ◽  
Marialaura Fanelli ◽  
...  
Keyword(s):  
Immune System ◽  
Blood Cells ◽  
Ex Vivo ◽  
Cell Subset ◽  
Adverse Outcomes ◽  
Cytokine Signaling ◽  
Cytokine Storm ◽  
Thymosin Alpha 1

Abstract COVID-19 is characterized by immune-mediated lung injury and complex alterations of the immune system, such as lymphopenia and cytokine storm, that have been associated with adverse outcomes underlining a fundamental role of host response in SARS-CoV-2 infection and the pathogenesis of the disease. Thymosin alpha 1 (Tα1) is one of the molecules used in the management of COVID-19, since it is known to restore the homeostasis of the immune system during infections and cancer. Here we captured the interconnected biological processes regulated by Tα1 in CD8+ T cells under inflammatory conditions. Genes associated with cytokine signaling and production were found up-regulated in blood cells from COVID-19 patients and the ex-vivo treatment with Tα1 mitigated cytokines expression and inhibited lymphocytes activation in CD8+ T cell subset specifically, suggesting the potential role of Tα1 in modulating the immune response homeostasis and the cytokine storm in vivo.

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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