scholarly journals Cynomolgus Monkey as an Emerging Animal Model to Study Drug Transporters: In Vitro, In Vivo, In Vitro-To-In Vivo Translation

2021 ◽  
pp. DMD-MR-2021-000695
Author(s):  
Hong Shen ◽  
Zheng Yang ◽  
A. David Rodrigues
Keyword(s):  
Animal Model ◽  
Cynomolgus Monkey ◽  
Drug Transporters ◽  
Study Drug

scholarly journals Preclinical Testing of Radiopharmaceuticals for the Detection and Characterization of Osteomyelitis: Experiences from a Porcine Model

Molecules ◽  
2021 ◽  
Vol 26 (14) ◽  
pp. 4221
Author(s):  
Aage Kristian Olsen Alstrup ◽  
Svend Borup Jensen ◽  
Ole Lerberg Nielsen ◽  
Lars Jødal ◽  
Pia Afzelius
Keyword(s):  
Animal Model ◽  
Animal Models ◽  
Porcine Model ◽  
Animal Experiments ◽  
Radioactive Tracers ◽  
The Individual ◽  
Selection Of

The development of new and better radioactive tracers capable of detecting and characterizing osteomyelitis is an ongoing process, mainly because available tracers lack selectivity towards osteomyelitis. An integrated part of developing new tracers is the performance of in vivo tests using appropriate animal models. The available animal models for osteomyelitis are also far from ideal. Therefore, developing improved animal osteomyelitis models is as important as developing new radioactive tracers. We recently published a review on radioactive tracers. In this review, we only present and discuss osteomyelitis models. Three ethical aspects (3R) are essential when exposing experimental animals to infections. Thus, we should perform experiments in vitro rather than in vivo (Replacement), use as few animals as possible (Reduction), and impose as little pain on the animal as possible (Refinement). The gain for humans should by far exceed the disadvantages for the individual experimental animal. To this end, the translational value of animal experiments is crucial. We therefore need a robust and well-characterized animal model to evaluate new osteomyelitis tracers to be sure that unpredicted variation in the animal model does not lead to a misinterpretation of the tracer behavior. In this review, we focus on how the development of radioactive tracers relies heavily on the selection of a reliable animal model, and we base the discussions on our own experience with a porcine model.

scholarly journals A Novel Infection Protocol in Zebrafish Embryo to Assess Pseudomonas aeruginosa Virulence and Validate Efficacy of a Quorum Sensing Inhibitor In Vivo

Pathogens ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 401
Author(s):  
Pauline Nogaret ◽  
Fatima El El Garah ◽  
Anne-Béatrice Blanc-Potard
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Animal Model ◽  
Quorum Sensing ◽  
Drug Testing ◽  
Drug Efficacy ◽  
Embryo Viability ◽  
Immersion Method ◽  
Opportunistic Human Pathogen

The opportunistic human pathogen Pseudomonas aeruginosa is responsible for a variety of acute infections and is a major cause of mortality in chronically infected cystic fibrosis patients. Due to increased resistance to antibiotics, new therapeutic strategies against P. aeruginosa are urgently needed. In this context, we aimed to develop a simple vertebrate animal model to rapidly assess in vivo drug efficacy against P. aeruginosa. Zebrafish are increasingly considered for modeling human infections caused by bacterial pathogens, which are commonly microinjected in embryos. In the present study, we established a novel protocol for zebrafish infection by P. aeruginosa based on bath immersion in 96-well plates of tail-injured embryos. The immersion method, followed by a 48-hour survey of embryo viability, was first validated to assess the virulence of P. aeruginosa wild-type PAO1 and a known attenuated mutant. We then validated its relevance for antipseudomonal drug testing by first using a clinically used antibiotic, ciprofloxacin. Secondly, we used a novel quorum sensing (QS) inhibitory molecule, N-(2-pyrimidyl)butanamide (C11), the activity of which had been validated in vitro but not previously tested in any animal model. A significant protective effect of C11 was observed on infected embryos, supporting the ability of C11 to attenuate in vivo P. aeruginosa pathogenicity. In conclusion, we present here a new and reliable method to compare the virulence of P. aeruginosa strains in vivo and to rapidly assess the efficacy of clinically relevant drugs against P. aeruginosa, including new antivirulence compounds.

In Vitro and In Vivo Assessment of Renal Drug Transporters in the Disposition of Mesna and Dimesna

2012 ◽  
Vol 52 (4) ◽  
pp. 530-542 ◽  
Author(s):  
M. J. Cutler ◽  
B. L. Urquhart ◽  
T. J. Velenosi ◽  
H. E. Meyer zu Schwabedissen ◽  
G. K. Dresser ◽  
...  
Keyword(s):  
Drug Transporters ◽  
In Vivo Assessment

scholarly journals Photopolymerizable Injectable Cartilage Mimetic Hydrogel for the Treatment of Focal Chondral Lesions: A Proof of Concept Study in a Rabbit Animal Model

2018 ◽  
Vol 47 (1) ◽  
pp. 212-221 ◽  
Author(s):  
Cecilia Pascual-Garrido ◽  
Elizabeth A. Aisenbrey ◽  
Francisco Rodriguez-Fontan ◽  
Karin A. Payne ◽  
Stephanie J. Bryant ◽  
...  
Keyword(s):  
Animal Model ◽  
Chondrogenic Differentiation ◽  
Osteochondral Lesions ◽  
Chondral Defect ◽  
Group A ◽  
Group B ◽  
Safranin O

Background: In this study, we investigate the in vitro and in vivo chondrogenic capacity of a novel photopolymerizable cartilage mimetic hydrogel, enhanced with extracellular matrix analogs, for cartilage regeneration. Purpose: To (1) determine whether mesenchymal stem cells (MSCs) embedded in a novel cartilage mimetic hydrogel support in vitro chondrogenesis, (2) demonstrate that the proposed hydrogel can be delivered in situ in a critical chondral defect in a rabbit model, and (3) determine whether the hydrogel with or without MSCs supports in vivo chondrogenesis in a critical chondral defect. Study Design: Controlled laboratory study. Methods: Rabbit bone marrow–derived MSCs were isolated, expanded, encapsulated in the hydrogel, and cultured in chondrogenic differentiation medium for 9 weeks. Compressive modulus was evaluated at day 1 and at weeks 3, 6, and 9. Chondrogenic differentiation was investigated via quantitative polymerase reaction, safranin-O staining, and immunofluorescence. In vivo, a 3 mm–wide × 2-mm-deep chondral defect was created bilaterally on the knee trochlea of 10 rabbits. Each animal had 1 defect randomly assigned to be treated with hydrogel with or without MSCs, and the contralateral knee was left untreated. Hence, each rabbit served as its own matched control. Three groups were established: group A, hydrogel (n = 5); group B, hydrogel with MSCs (n = 5); and group C, control (n = 10). Repair tissue was evaluated at 6 months after intervention. Results: In vitro, chondrogenesis and the degradable behavior of the hydrogel by MSCs were confirmed. In vivo, the hydrogel could be delivered intraoperatively in a sterile manner. Overall, the hydrogel group had the highest scores on the modified O’Driscoll scoring system (group A, 17.4 ± 4.7; group B, 13 ± 3; group C, 16.7 ± 2.9) ( P = .11) and showed higher safranin-O staining (group A, 49.4% ± 20%; group B, 25.8% ± 16.4%; group C, 36.9% ± 25.2%) ( P = .27), although significance was not detected for either parameter. Conclusion: This study provides the first evidence of the ability to photopolymerize this novel hydrogel in situ and assess its ability to provide chondrogenic cues for cartilage repair in a small animal model. In vitro chondrogenesis was evident when MSCs were encapsulated in the hydrogel. Clinical Relevance: Cartilage mimetic hydrogel may offer a tissue engineering approach for the treatment of osteochondral lesions.

Effect of Auraptene on angiogenesis in Xenograft model of breast cancer

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Mohammad Reza Shiran ◽  
Elham Mahmoudian ◽  
Abolghasem Ajami ◽  
Seyed Mostafa Hosseini ◽  
Ayjamal Khojasteh ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Animal Model ◽  
Protein Expression ◽  
Western Blot ◽  
Xenograft Model ◽  
Dependent Manner ◽  
Concentration Dependent Manner

Abstract Objectives Angiogenesis is the most important challenge in breast cancer treatment. Recently, scientists become interesting in rare natural products and intensive researches was performed to identify their pharmacological profile. Auraptene shows helpful effects such as cancer chemo-preventive, anti-inflammatory, anti-oxidant, immuno-modulatory. In this regard, we investigated the anti-angiogenesis effect of Auraptene in in-vitro and in-vivo model of breast cancer. Methods In this study, 4T, MDA-MB-231 and HUVEC cell lines were used. The proliferation study was done by MTT assay. For tube formation assay, 250 matrigel, 1 × 104 HUVEC treated with Auraptene, 20 ng/mL EGF, 20 ng/mL bFGF and 20 ng/mL VEGF were used. Gene expression of important gene related to angiogenesis in animal model of breast cancer was investigated by Real-time PCR. Protein expression of VCAM-1 and TNFR-1 gene related to angiogenesis in animal model of breast cancer was investigated by western-blot. Results Auraptene treatment led to reduction in cell viability of MDA-MB-231 in a concentration-dependent manner. Also, we observed change in the number of tubes or branches formed by cells incubated with 40 and 80 μM Auraptene. Auraptene effect the gene expression of important gene related to angiogenesis (VEGF, VEGFR2, COX2, IFNɣ). Moreover, the western blot data exhibited that Auraptene effect the protein expression of VCAM-1 and TNFR-1. Conclusions Overall, this study shows that Auraptene significantly suppressed angiogenesis via down-regulation of VEGF, VEGFR2, VCAM-1, TNFR-1, COX-2 and up-regulation of IFNγ.

scholarly journals Impact of Bacterial Biofilm Formation on In Vitro and In Vivo Activities of Antibiotics

1998 ◽  
Vol 42 (4) ◽  
pp. 895-898 ◽  
Author(s):  
Silvia Schwank ◽  
Zarko Rajacic ◽  
Werner Zimmerli ◽  
Jürg Blaser
Keyword(s):  
Animal Model ◽  
Staphylococcus Epidermidis ◽  
Biofilm Formation ◽  
Bacterial Biofilm ◽  
Phenotypic Resistance ◽  
Vitro Model ◽  
The Impact ◽  
Isogenic Strains

ABSTRACT The impact of bacterial adherence on antibiotic activity was analyzed with two isogenic strains of Staphylococcus epidermidis that differ in the features of their in vitro biofilm formation. The eradication of bacteria adhering to glass beads by amikacin, levofloxacin, rifampin, or teicoplanin was studied in an animal model and in a pharmacokinetically matched in vitro model. The features of S. epidermidis RP62A that allowed it to grow on surfaces in multiple layers promoted phenotypic resistance to antibiotic treatment, whereas strain M7 failed to accumulate, despite initial adherence on surfaces and growth in suspension similar to those for RP62A. Biofilms of S. epidermidis M7 were better eradicated than those of strain RP62A in vitro (46 versus 31%;P < 0.05) as well as in the animal model (39 versus 9%; P < 0.01).

In vitro culture of cynomolgus monkey embryos beyond early gastrulation

Science ◽  
2019 ◽  
Vol 366 (6467) ◽  
pp. eaax7890 ◽  
Author(s):  
Huaixiao Ma ◽  
Jinglei Zhai ◽  
Haifeng Wan ◽  
Xiangxiang Jiang ◽  
Xiaoxiao Wang ◽  
...  
Keyword(s):  
In Vitro Culture ◽  
Cynomolgus Monkey ◽  
Primordial Germ Cells ◽  
Lineage Specification ◽  
Single Cell Rna Sequencing ◽  
Human Embryogenesis ◽  
Key Events ◽  
Anterior Posterior

Gastrulation is a key event in embryonic development when the germ layers are specified and the basic animal body plan is established. The complexities of primate gastrulation remain a mystery because of the difficulties in accessing primate embryos at this stage. Here, we report the establishment of an in vitro culture (IVC) system that supports the continuous development of cynomolgus monkey blastocysts beyond early gastrulation up to 20 days after fertilization. The IVC embryos highly recapitulated the key events of in vivo early postimplantation development, including segregation of the epiblast and hypoblast, formation of the amniotic and yolk sac cavities, appearance of the primordial germ cells, and establishment of the anterior-posterior axis. Single-cell RNA-sequencing analyses of the IVC embryos provide information about lineage specification during primate early postimplantation development. This system provides a platform with which to explore the characteristics and mechanisms of early postimplantation embryogenesis in primates with possible conservation of cell movements and lineages in human embryogenesis.

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