scholarly journals Iterative Cellular Screening System for Nanoparticle Safety Testing

2015 ◽  
Vol 2015 ◽  
pp. 1-16 ◽  
Author(s):  
Franziska Sambale ◽  
Frank Stahl ◽  
Ferdinand Rüdinger ◽  
Dror Seliktar ◽  
Cornelia Kasper ◽  
...  

Nanoparticles have the potential to exhibit risks to human beings and to the environment; due to the wide applications of nanoproducts, extensive risk management must not be neglected. Therefore, we have constructed a cell-based, iterative screening system to examine a variety of nanoproducts concerning their toxicity during development. The sensitivity and application of various cell-based methods were discussed and proven by applying the screening to two different nanoparticles: zinc oxide and titanium dioxide nanoparticles. They were used as benchmarks to set up our methods and to examine their effects on mammalian cell lines. Different biological processes such as cell viability, gene expression of interleukin-8 and heat shock protein 70, as well as morphology changes were investigated. Within our screening system, both nanoparticle suspensions and coatings can be tested. Electric cell impedance measurements revealed to be a good method for online monitoring of cellular behavior. The implementation of three-dimensional cell culture is essential to better mimicin vivoconditions. In conclusion, our screening system is highly efficient, cost minimizing, and reduces the need for animal studies.

2017 ◽  
Vol 10 (03) ◽  
pp. 1750003 ◽  
Author(s):  
Shuang Zhang ◽  
Chengcai Leng ◽  
Hongbo Liu ◽  
Kun Wang ◽  
Jie Tian

Bioluminescence tomography (BLT) is a novel optical molecular imaging technique that advanced the conventional planar bioluminescence imaging (BLI) into a quantifiable three-dimensional (3D) approach in preclinical living animal studies in oncology. In order to solve the inverse problem and reconstruct tumor lesions inside animal body accurately, the prior structural information is commonly obtained from X-ray computed tomography (CT). This strategy requires a complicated hybrid imaging system, extensive post imaging analysis and involvement of ionizing radiation. Moreover, the overall robustness highly depends on the fusion accuracy between the optical and structural information. Here, we present a pure optical bioluminescence tomographic (POBT) system and a novel BLT workflow based on multi-view projection acquisition and 3D surface reconstruction. This method can reconstruct the 3D surface of an imaging subject based on a sparse set of planar white-light and bioluminescent images, so that the prior structural information can be offered for 3D tumor lesion reconstruction without the involvement of CT. The performance of this novel technique was evaluated through the comparison with a conventional dual-modality tomographic (DMT) system and a commercialized optical imaging system (IVIS Spectrum) using three breast cancer xenografts. The results revealed that the new technique offered comparable in vivo tomographic accuracy with the DMT system ([Formula: see text]) in much shorter data analysis time. It also offered significantly better accuracy comparing with the IVIS system ([Formula: see text]) without sacrificing too much time.


1974 ◽  
Vol 77 (1_Suppla) ◽  
pp. S409-S422 ◽  
Author(s):  
Robert Gordon McConnell

ABSTRACT Intrauterine devices (IUD's), intrauterine drug reservoirs (IUDR's), and metal-releasing intrauterine drug reservoirs (MR-IUDR's) with antifertility activity in the animal and human are considered as separate entities. General requirements for toxicologic and teratologic testing of such agents in animals are presented. A comparison reveals the relative advantages and disadvantages of simian, canine, lagomorph, and rodent species. A pretreatment review of obstetric-gynaecologic status and history of each animal is emphasized. Designing of appropriate replicas of the clinical device for use in predictive animal studies requires comparative data on uterine morphology, device-endometrium spatial relationships, and drug release rates. Adult, maternal and foetal tissue metal levels may be important; the analytical methods for detecting and localizing cellular and subcellular wet tissue metal levels are available. Existing in vivo mutagenicity assay procedures are poorly adapted to intrauterine drug testing. Method modifications are explored briefly. A sequence for the animal safety testing of an intrauterine antifertility agent, and its interrelation with clinical research, is outlined.


Materials ◽  
2022 ◽  
Vol 15 (1) ◽  
pp. 318
Author(s):  
Saeid Kargozar ◽  
Peiman Brouki Milan ◽  
Moein Amoupour ◽  
Farzad Kermani ◽  
Sara Gorgani ◽  
...  

The use of bioactive glasses (BGs) has been quite fruitful in hard tissue engineering due to the capability of these materials to bond to living bone. In this work, a melt-derived magnesium (Mg)-doped BG (composition: 45SiO2–3P2O5–26CaO–15Na2O–7MgO–4K2O (mol.%)) was synthesized for being used in bone reconstruction. The prepared BGs were then manufactured as three-dimensional (3D) scaffolds by using the sponge replica approach. The microstructure of the samples was assessed by X-ray diffraction (XRD) and the surface morphology was observed by using scanning electron microscopy (SEM). The in vitro bioactivity and the release of osteo-stimulatory Mg2+ ions from the prepared samples were investigated over 7 days of incubation in simulated body fluids (SBF). In vitro cellular analyses revealed the compatibility of the Mg-doped BGs with human osteosarcoma cells (MG-63 cell line). Moreover, the Mg-doped BGs could induce bone nodule formation in vitro and improve the migratory ability of human umbilical vein endothelial cells (HUVECs). In vivo osteogenic capacity was further evaluated by implanting the BG-derived scaffolds into surgically-created critical-size bone defects in rats. Histological and immunohistological observations revealed an appropriate bone regeneration in the animals receiving the glass-based scaffolds after 12 weeks of surgery. In conclusion, our study indicates the effectiveness of the Mg-doped BGs in stimulating osteogenesis in both in vitro and in vivo conditions.


Author(s):  
Shaistha Saba

Abstract: Papaya (Carica papaya) is a tropical fruit having commercial importance because of its high nutritive and medicinal value. Papaya seeds are traditionally used by human beings from centuries to heal many illnesses. Papaya seeds contains antioxidants and antimicrobial virtues which gives protection against harmful free radicals and reduce rate of cancer and heart disease. Papaya seeds contain a variety of essential macro and micronutrients. The papaya seeds contain large amounts of nutrients, including fibre which is effective for combating constipation and other digestive problems. Seeds can be used to treat health complications such as urinary tract infection, candidiasis and sepsis. Papaya seeds are sometimes used in salads and can even be used as a substitute for black pepper. Products developed from papaya seeds are considered to be nutritionally rich with diverse sources of all nutrients. Papaya seeds have the potential to produce oil with nutritional and functional properties highly similar to olive oil. The papaya seed, and products may be useful for bio-fuel, medicinal and industrial purposes. Therefore, Papaya seeds are usually thrown away but their proper utilization can lead to the development of novel drug in medicine and considered as safe for consumption. ‘In this review subtopics covered are nutritional and Phytochemicals composition, antioxidant effect, antibacterial Activity, anthelminthic effect, Phytochemicals with Anticancer activity, Lycopene and isothiocyanate applications in papaya, papaya seed products and in vivo animal studies.’


Polymers ◽  
2020 ◽  
Vol 12 (8) ◽  
pp. 1782 ◽  
Author(s):  
Ali Smandri ◽  
Abid Nordin ◽  
Ng Min Hwei ◽  
Kok-Yong Chin ◽  
Izhar Abd Aziz ◽  
...  

Three-dimensional bioprinting has rapidly paralleled many biomedical applications and assisted in advancing the printing of complex human organs for a better therapeutic practice. The objective of this systematic review is to highlight evidence from the existing studies and evaluate the effectiveness of using natural-based bioinks in skin regeneration and wound healing. A comprehensive search of all relevant original articles was performed based on prespecified eligibility criteria. The search was carried out using PubMed, Web of Science, Scopus, Medline Ovid, and ScienceDirect. Eighteen articles fulfilled the inclusion and exclusion criteria. The animal studies included a total of 151 animals with wound defects. A variety of natural bioinks and skin living cells were implanted in vitro to give insight into the technique through different assessments and findings. Collagen and gelatin hydrogels were most commonly used as bioinks. The follow-up period ranged between one day and six weeks. The majority of animal studies reported that full wound closure was achieved after 2–4 weeks. The results of both in vitro cell culture and in vivo animal studies showed the positive impact of natural bioinks in promoting wound healing. Future research should be focused more on direct the bioprinting of skin wound treatments on animal models to open doors for human clinical trials.


Author(s):  
Indira Sigdel ◽  
Niraj Gupta ◽  
Fairuz Faizee ◽  
Vishwa M. Khare ◽  
Amit K. Tiwari ◽  
...  

Of around half a million women dying of breast cancer each year, more than 90% die due to metastasis. Models necessary to understand the metastatic process, particularly breast cancer cell extravasation and colonization, are currently limited and urgently needed to develop therapeutic interventions necessary to prevent breast cancer metastasis. Microfluidic approaches aim to reconstitute functional units of organs that cannot be modeled easily in traditional cell culture or animal studies by reproducing vascular networks and parenchyma on a chip in a three-dimensional, physiologically relevantin vitrosystem. In recent years, microfluidics models utilizing innovative biomaterials and micro-engineering technologies have shown great potential in our effort of mechanistic understanding of the breast cancer metastasis cascade by providing 3D constructs that can mimicin vivocellular microenvironment and the ability to visualize and monitor cellular interactions in real-time. In this review, we will provide readers with a detailed discussion on the application of the most up-to-date, state-of-the-art microfluidics-based breast cancer models, with a special focus on their application in the engineering approaches to recapitulate the metastasis process, including invasion, intravasation, extravasation, breast cancer metastasis organotropism, and metastasis niche formation.


Cells ◽  
2020 ◽  
Vol 9 (4) ◽  
pp. 1062 ◽  
Author(s):  
Michele Minopoli ◽  
Sabrina Sarno ◽  
Gioconda Di Carluccio ◽  
Rosa Azzaro ◽  
Susan Costantini ◽  
...  

Chondrosarcomas (CHS) are malignant cartilaginous neoplasms with diverse morphological features, characterized by resistance to chemo- and radiation therapies. In this study, we investigated the role of tumor-associated macrophages (TAM)s in tumor tissues from CHS patients by immunohistochemistry. Three-dimensional organotypic co-cultures were set up in order to evaluate the contribution of primary human CHS cells in driving an M2-like phenotype in monocyte-derived primary macrophages, and the capability of macrophages to promote growth and/or invasiveness of CHS cells. Finally, with an in vivo model of primary CHS cells engrafted in nude mice, we tested the ability of a potent peptide inhibitor of cell migration (Ac-d-Tyr-d-Arg-Aib-d-Arg-NH2, denoted RI-3) to reduce recruitment and infiltration of monocytes into CHS neoplastic lesions. We found a significant correlation between alternatively activated M2 macrophages and intratumor microvessel density in both conventional and dedifferentiated CHS human tissues, suggesting a link between TAM abundance and vascularization in CHS. In 3D and non-contact cu-culture models, soluble factors produced by CHS induced a M2-like phenotype in macrophages that, in turn, increased motility, invasion and matrix spreading of CHS cells. Finally, we present evidence that RI-3 successfully prevent both recruitment and infiltration of monocytes into CHS tissues, in nude mice.


2020 ◽  
Vol 8 (4) ◽  
pp. 504 ◽  
Author(s):  
Smriti Verma ◽  
Stefania Senger ◽  
Bobby J. Cherayil ◽  
Christina S. Faherty

The molecular complexity of host-pathogen interactions remains poorly understood in many infectious diseases, particularly in humans due to the limited availability of reliable and specific experimental models. To bridge the gap between classical two-dimensional culture systems, which often involve transformed cell lines that may not have all the physiologic properties of primary cells, and in vivo animal studies, researchers have developed the organoid model system. Organoids are complex three-dimensional structures that are generated in vitro from primary cells and can recapitulate key in vivo properties of an organ such as structural organization, multicellularity, and function. In this review, we discuss how organoids have been deployed in exploring Salmonella infection in mice and humans. In addition, we summarize the recent advancements that hold promise to elevate our understanding of the interactions and crosstalk between multiple cell types and the microbiota with Salmonella. These models have the potential for improving clinical outcomes and future prophylactic and therapeutic intervention strategies.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Rhiannon David ◽  
Sarah Gee ◽  
Kainat Khan ◽  
Amy Wilson ◽  
Ann Doherty

AbstractMicronucleus (MN) assessment is a valuable tool in safety assessment. However, several compounds are positive in the in vivo bone marrow (BM) MN assay but negative in vitro, reflecting that BM complexity is not recapitulated in vitro. Importantly, these compounds are not genotoxic; rather, drug-driven pharmacological-effects on the BM increase MN, however, without mechanistic understanding, in vivo positives stop drug-progression. Thus, physiologically-relevant BM models are required to bridge the gap between in vitro and in vivo. The current study aimed to investigate the utility of two human 3D BM models (fluidic and static) for MN assessment. MN induction following treatment with etoposide and Poly-ADP Ribose Polymerase inhibitor (PARPi) and prednisolone (negative in vitro, positive in vivo) was determined in 2D L5178Y and human BM cells, and the 3D BM models. Etoposide (0–0.070 µM) and PARPi (0–150 µM) induced MN in both 3D BM models indicating their utility for genotoxicity testing. Interestingly, PARPi treatment induced a MN trend in 3D more comparable to in vivo. Importantly, prednisolone (0–1.7 mM) induced MN in both 3D BM models, suggesting recapitulation of the in vivo microenvironment. These models could provide a valuable tool to follow up, and eventually predict, suspected pharmacological mechanisms, thereby reducing animal studies.


Author(s):  
D. Reis ◽  
B. Vian ◽  
J. C. Roland

Wall morphogenesis in higher plants is a problem still open to controversy. Until now the possibility of a transmembrane control and the involvement of microtubules were mostly envisaged. Self-assembly processes have been observed in the case of walls of Chlamydomonas and bacteria. Spontaneous gelling interactions between xanthan and galactomannan from Ceratonia have been analyzed very recently. The present work provides indications that some processes of spontaneous aggregation could occur in higher plants during the formation and expansion of cell wall.Observations were performed on hypocotyl of mung bean (Phaseolus aureus) for which growth characteristics and wall composition have been previously defined.In situ, the walls of actively growing cells (primary walls) show an ordered three-dimensional organization (fig. 1). The wall is typically polylamellate with multifibrillar layers alternately transverse and longitudinal. Between these layers intermediate strata exist in which the orientation of microfibrils progressively rotates. Thus a progressive change in the morphogenetic activity occurs.


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