546. A New Ex-Vivo Approach Using Autologous Dermal Fibroblasts Expressing hLMP3 Induces Bone Formation and Bone Healing in Animal Models

Osteotomy is a common step in oncological, reconstructive, and trauma surgery. Drilling and elevated temperature during osteotomy produce thermal osteonecrosis. Heat and associated mechanical damage during osteotomy can impair bone healing, with consequent failure of fracture fixation or dental implants. Several ex vivo studies on animal bone were recently focused on heating production during osteotomy with conventional drill and piezoelectric devices, particularly in endosseous dental implant sites. The current literature on bone drilling and osteotomic surface analysis is here reviewed and the dynamics of bone healing after osteotomy with traditional and piezoelectric devices are discussed. Moreover, the methodologies involved in the experimental osteotomy and clinical studies are compared, focusing on ex vivo and in vivo findings.

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An Overview of Methods Used To Clarify Pathogenesis Mechanisms of Campylobacter jejuni

Journal of Food Protection ◽

10.4315/0362-028x-73.4.786 ◽

2010 ◽

Vol 73 (4) ◽

pp. 786-802 ◽

Cited By ~ 13

Author(s):

N. HADDAD ◽

C. MARCE ◽

C. MAGRAS ◽

J.-M. CAPPELIER

Keyword(s):

Animal Models ◽

Molecular Biology ◽

Campylobacter Jejuni ◽

Ex Vivo ◽

Current Model ◽

Toxin Production ◽

Eukaryotic Cell ◽

Host Interactions ◽

Lower Intestine ◽

Ex Vivo Approach

Thermotolerant campylobacters are the most frequent cause of bacterial infection of the lower intestine worldwide. The mechanism of pathogenesis of Campylobacter jejuni comprises four main stages: adhesion to intestinal cells, colonization of the digestive tract, invasion of targeted cells, and toxin production. In response to the high number of cases of human campylobacteriosis, various virulence study models are available according to the virulence stage being analyzed. The aim of this review is to compare the different study models used to look at human disease. Molecular biology tools used to identify genes or proteins involved in virulence mechanisms are also summarized. Despite high cost and limited availability, animal models are frequently used to study digestive disease, in particular to analyze the colonization stage. Eukaryotic cell cultures have been developed because of fewer restrictions on their use and the lower cost of these cultures compared with animal models, and this ex vivo approach makes it possible to mimic the bacterial cell–host interactions observed in natural disease cases. Models are complemented by molecular biology tools, especially mutagenesis and DNA microarray methods to identify putative virulence genes or proteins and permit their characterization. No current model seems to be ideal for studying the complete range of C. jejuni virulence. However, the models available deal with different aspects of the complex pathogenic mechanisms particular to this bacterium.

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702. Cell-Based Ex Vivo Gene Therapy with BMP2 Gene Transduced Dermal Fibroblasts To Accelerate Bone Healing in Equine Model

Molecular Therapy ◽

10.1016/s1525-0016(16)39060-8 ◽

2009 ◽

Vol 17 ◽

pp. S268-S269

Keyword(s):

Gene Therapy ◽

Bone Healing ◽

Ex Vivo ◽

Dermal Fibroblasts ◽

Ex Vivo Gene Therapy

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Synaptic Reshaping and Neuronal Outcomes in the Temporal Lobe Epilepsy

International Journal of Molecular Sciences ◽

10.3390/ijms22083860 ◽

2021 ◽

Vol 22 (8) ◽

pp. 3860

Author(s):

Elisa Ren ◽

Giulia Curia

Keyword(s):

Animal Models ◽

Temporal Lobe Epilepsy ◽

Temporal Lobe ◽

Current Knowledge ◽

Focal Epilepsy ◽

Ex Vivo ◽

Hippocampal Sclerosis ◽

Control Group ◽

Epileptogenic Zone ◽

Epileptiform Discharges

Temporal lobe epilepsy (TLE) is one of the most common types of focal epilepsy, characterized by recurrent spontaneous seizures originating in the temporal lobe(s), with mesial TLE (mTLE) as the worst form of TLE, often associated with hippocampal sclerosis. Abnormal epileptiform discharges are the result, among others, of altered cell-to-cell communication in both chemical and electrical transmissions. Current knowledge about the neurobiology of TLE in human patients emerges from pathological studies of biopsy specimens isolated from the epileptogenic zone or, in a few more recent investigations, from living subjects using positron emission tomography (PET). To overcome limitations related to the use of human tissue, animal models are of great help as they allow the selection of homogeneous samples still presenting a more various scenario of the epileptic syndrome, the presence of a comparable control group, and the availability of a greater amount of tissue for in vitro/ex vivo investigations. This review provides an overview of the structural and functional alterations of synaptic connections in the brain of TLE/mTLE patients and animal models.

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Antiangiogenic effects of phospholipase A2 Lys49 BnSP-7 from Bothrops pauloensis snake venom on endothelial cells: An in vitro and ex vivo approach

Toxicology in Vitro ◽

10.1016/j.tiv.2021.105099 ◽

2021 ◽

Vol 72 ◽

pp. 105099

Author(s):

Lorena Polloni ◽

Fernanda Van Petten Vasconcelos Azevedo ◽

Samuel Cota Teixeira ◽

Eloá Moura ◽

Tassia Rafaela Costa ◽

...

Keyword(s):

Endothelial Cells ◽

Phospholipase A2 ◽

Snake Venom ◽

Ex Vivo ◽

Ex Vivo Approach

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Ibudilast Mitigates Delayed Bone Healing Caused by Lipopolysaccharide by Altering Osteoblast and Osteoclast Activity

International Journal of Molecular Sciences ◽

10.3390/ijms22031169 ◽

2021 ◽

Vol 22 (3) ◽

pp. 1169

Author(s):

Yuhan Chang ◽

Chih-Chien Hu ◽

Ying-Yu Wu ◽

Steve W. N. Ueng ◽

Chih-Hsiang Chang ◽

...

Keyword(s):

Cell Wall ◽

Bone Formation ◽

Cancellous Bone ◽

Bone Healing ◽

Bone Bridge ◽

Cell Wall Components ◽

Osteoclast Activity ◽

Wall Components

Bacterial infection in orthopedic surgery is challenging because cell wall components released after bactericidal treatment can alter osteoblast and osteoclast activity and impair fracture stability. However, the precise effects and mechanisms whereby cell wall components impair bone healing are unclear. In this study, we characterized the effects of lipopolysaccharide (LPS) on bone healing and osteoclast and osteoblast activity in vitro and in vivo and evaluated the effects of ibudilast, an antagonist of toll-like receptor 4 (TLR4), on LPS-induced changes. In particular, micro-computed tomography was used to reconstruct femoral morphology and analyze callus bone content in a femoral defect mouse model. In the sham-treated group, significant bone bridge and cancellous bone formation were observed after surgery, however, LPS treatment delayed bone bridge and cancellous bone formation. LPS inhibited osteogenic factor-induced MC3T3-E1 cell differentiation, alkaline phosphatase (ALP) levels, calcium deposition, and osteopontin secretion and increased the activity of osteoclast-associated molecules, including cathepsin K and tartrate-resistant acid phosphatase in vitro. Finally, ibudilast blocked the LPS-induced inhibition of osteoblast activation and activation of osteoclast in vitro and attenuated LPS-induced delayed callus bone formation in vivo. Our results provide a basis for the development of a novel strategy for the treatment of bone infection.

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Ex vivo approach supports both direct and indirect actions of melatonin on immunity in pike-perch Sander lucioperca

Fish & Shellfish Immunology ◽

10.1016/j.fsi.2021.03.005 ◽

2021 ◽

Author(s):

Sébastien Baekelandt ◽

Valérie Cornet ◽

Syaghalirwa.N.M. Mandiki ◽

Lambert Jérôme ◽

Dubois Mickaël ◽

...

Keyword(s):

Ex Vivo ◽

Sander Lucioperca ◽

Pike Perch ◽

Ex Vivo Approach

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Unraveling the In Vivo Protein Corona

Cells ◽

10.3390/cells10010132 ◽

2021 ◽

Vol 10 (1) ◽

pp. 132

Author(s):

Johanna Simon ◽

Gabor Kuhn ◽

Michael Fichter ◽

Stephan Gehring ◽

Katharina Landfester ◽

...

Keyword(s):

Plasma Proteins ◽

Ex Vivo ◽

Protein Corona ◽

Blood Proteins ◽

Therapeutic Application ◽

Complex Situation ◽

Ex Vivo Approach ◽

In Vivo Administration

Understanding the behavior of nanoparticles upon contact with a physiological environment is of urgent need in order to improve their properties for a successful therapeutic application. Most commonly, the interaction of nanoparticles with plasma proteins are studied under in vitro conditions. However, this has been shown to not reflect the complex situation after in vivo administration. Therefore, here we focused on the investigation of magnetic nanoparticles with blood proteins under in vivo conditions. Importantly, we observed a radically different proteome in vivo in comparison to the in vitro situation underlining the significance of in vivo protein corona studies. Next to this, we found that the in vivo corona profile does not significantly change over time. To mimic the in vivo situation, we established an approach, which we termed “ex vivo” as it uses whole blood freshly prepared from an animal. Overall, we present a comprehensive analysis focusing on the interaction between nanoparticles and blood proteins under in vivo conditions and how to mimic this situation with our ex vivo approach. This knowledge is needed to characterize the true biological identity of nanoparticles.

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Bone Morphogenetic Proteins, Carriers, and Animal Models in the Development of Novel Bone Regenerative Therapies

Materials ◽

10.3390/ma14133513 ◽

2021 ◽

Vol 14 (13) ◽

pp. 3513

Author(s):

Nikola Stokovic ◽

Natalia Ivanjko ◽

Drazen Maticic ◽

Frank P. Luyten ◽

Slobodan Vukicevic

Keyword(s):

Animal Models ◽

Bone Formation ◽

Bone Morphogenetic Proteins ◽

Animal Experiments ◽

Inorganic Materials ◽

New Bone Formation ◽

Segmental Bone ◽

Posterolateral Spinal Fusion ◽

Regenerative Therapies ◽

Observation Period

Bone morphogenetic proteins (BMPs) possess a unique ability to induce new bone formation. Numerous preclinical studies have been conducted to develop novel, BMP-based osteoinductive devices for the management of segmental bone defects and posterolateral spinal fusion (PLF). In these studies, BMPs were combined with a broad range of carriers (natural and synthetic polymers, inorganic materials, and their combinations) and tested in various models in mice, rats, rabbits, dogs, sheep, and non-human primates. In this review, we summarized bone regeneration strategies and animal models used for the initial, intermediate, and advanced evaluation of promising therapeutical solutions for new bone formation and repair. Moreover, in this review, we discuss basic aspects to be considered when planning animal experiments, including anatomical characteristics of the species used, appropriate BMP dosing, duration of the observation period, and sample size.

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Abstract 3680: Transfusion-Induced Tissue Hypoxia is Ameliorated by S -nitrosohemoglobin Repletion of Stored Red Blood Cells

Circulation ◽

10.1161/circ.118.suppl_18.s_465-a ◽

2008 ◽

Vol 118 (suppl_18) ◽

Author(s):

Diana L Diesen ◽

Jonathan S Stamler

Keyword(s):

Animal Models ◽

Red Blood Cells ◽

Blood Cells ◽

Tissue Oxygenation ◽

Ex Vivo ◽

Tissue Hypoxia ◽

Mouse Blood ◽

Mortality And Morbidity ◽

Stored Blood ◽

Related Mortality

Transfusion of stored red blood cells (RBCs) is associated with a decrease in tissue oxygenation in animal models and with increased mortality and morbidity in patients. Recent studies have demonstrated that stored RBCs are deficient in vasodilatory ability and depleted of S -nitrosohemoglobin (SNO-Hb), and that renitrosylation ex vivo can increase SNO-Hb levels and restore vasoactivity. We have examined in a mouse model the extent to which transfusion impairs tissue oxygenation and whether SNO-Hb repletion can ameliorate that impairment. We report here that transfusion of (mouse) RBCs stored for 1 day or 1 week results in tissue hypoxia that is largely prevented by SNO-Hb repletion prior to transfusion ( 1 day stored blood : % decrease in oxygenation 58+/−10% untreated vs. 92+/−0.7% SNO-Hb repleted, p<0.05, n=3– 6; 1 week stored blood : % decrease in oxygenation 66+/−10% untreated vs. 91+/−2.8% SNO-Hb repleted, p<0.05, n=3– 6). Storage of mouse blood beyond human expiration-equivalents (1 month) resulted in substantial lysis and the death of all mice transfused (native and SNO-Hb repleted blood, n=5). In conclusion, repletion of SNO-Hb ameliorates the decrease in tissue oxygenation that results from transfusion of untreated stored blood. Therefore, SNO-Hb repletion may provide a simple and efficacious method to reduce transfusion-related mortality and morbidity.

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