scholarly journals Development of a functional salivary gland tissue chip with potential for high-content drug screening

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Yuanhui Song ◽  
Hitoshi Uchida ◽  
Azmeer Sharipol ◽  
Lindsay Piraino ◽  
Jared A. Mereness ◽  
...  
Keyword(s):  
Salivary Gland ◽  
Salivary Glands ◽  
Drug Screening ◽  
Drug Testing ◽  
In Vitro Models ◽  
High Throughput Drug Screening ◽  
Array Technology ◽  
Gland Function ◽  
Poly Ethylene

AbstractRadiation therapy for head and neck cancers causes salivary gland dysfunction leading to permanent xerostomia. Limited progress in the discovery of new therapeutic strategies is attributed to the lack of in vitro models that mimic salivary gland function and allow high-throughput drug screening. We address this limitation by combining engineered extracellular matrices with microbubble (MB) array technology to develop functional tissue mimetics for mouse and human salivary glands. We demonstrate that mouse and human salivary tissues encapsulated within matrix metalloproteinase-degradable poly(ethylene glycol) hydrogels formed in MB arrays are viable, express key salivary gland markers, and exhibit polarized localization of functional proteins. The salivary gland mimetics (SGm) respond to calcium signaling agonists and secrete salivary proteins. SGm were then used to evaluate radiosensitivity and mitigation of radiation damage using a radioprotective compound. Altogether, SGm exhibit phenotypic and functional parameters of salivary glands, and provide an enabling technology for high-content/throughput drug testing.

scholarly journals Sox9+ Cell is Required for Salivary Gland Regeneration after Radiation Damage via Wnt/β-Catenin Pathway

2021 ◽  
Author(s):  
Xiuyun Xu ◽  
Xiong Gan ◽  
Ming Zhang ◽  
Jiaxiang Xie ◽  
Shuang Chen ◽  
...  
Keyword(s):  
Salivary Gland ◽  
Salivary Glands ◽  
Cell Lineage ◽  
Term Treatment ◽  
Sequencing Data ◽  
Long Term Treatment ◽  
Radiation Induced ◽  
Gland Function ◽  
Salivary Gland Regeneration

Abstract Background: Radiotherapy for head and neck cancer can cause serious side effects, including severe damage to the salivary glands, resulting in symptoms such as xerostomia, dental caries, oral infectious and so on. Due to lack of long-term treatment for the symptoms of saliva barren, current research has focused on finding endogenous stem cells that can differentiate into various cell lineage to replace lost tissue and restore function. Results: In our study, we identified Sox9+ cells can differentiate into various salivary epithelial cell lineages under homeostatic conditions. After ablating Sox9+ cells, the salivary glands of irradiated mice showed more severe phenotypes and reduced proliferative capacity. Analysis of online single cell RNA-sequencing data revealed enrichment of the Wnt/β-catenin pathway in Sox9+ cell population. Furthermore, treatment of Wnt/β-catenin inhibitor to irradiated mice inhibited the regenerative capability of Sox9+ cells. Finally, we showed that Sox9+ cells were able to form organoids in vitro and transplanting these organoids into salivary glands after radiation restored part of salivary gland function. Conclusions: In short, our research indicated that regenerative therapy targeting Sox9+ cells is a promising method to solve the radiation induced salivary gland injury.

scholarly journals The Current Challenges for Drug Discovery in CNS Remyelination

2021 ◽  
Vol 22 (6) ◽  
pp. 2891
Author(s):  
Sonia Balestri ◽  
Alice Del Giovane ◽  
Carola Sposato ◽  
Marta Ferrarelli ◽  
Antonella Ragnini-Wilson
Keyword(s):  
Drug Screening ◽  
Myelin Sheath ◽  
Time Window ◽  
In Vitro Models ◽  
Adult Brain ◽  
Pharmacological Intervention ◽  
Cellular Models ◽  
New Findings ◽  
Myelin Injury

The myelin sheath wraps around axons, allowing saltatory currents to be transmitted along neurons. Several genetic, viral, or environmental factors can damage the central nervous system (CNS) myelin sheath during life. Unless the myelin sheath is repaired, these insults will lead to neurodegeneration. Remyelination occurs spontaneously upon myelin injury in healthy individuals but can fail in several demyelination pathologies or as a consequence of aging. Thus, pharmacological intervention that promotes CNS remyelination could have a major impact on patient’s lives by delaying or even preventing neurodegeneration. Drugs promoting CNS remyelination in animal models have been identified recently, mostly as a result of repurposing phenotypical screening campaigns that used novel oligodendrocyte cellular models. Although none of these have as yet arrived in the clinic, promising candidates are on the way. Many questions remain. Among the most relevant is the question if there is a time window when remyelination drugs should be administrated and why adult remyelination fails in many neurodegenerative pathologies. Moreover, a significant challenge in the field is how to reconstitute the oligodendrocyte/axon interaction environment representative of healthy as well as disease microenvironments in drug screening campaigns, so that drugs can be screened in the most appropriate disease-relevant conditions. Here we will provide an overview of how the field of in vitro models developed over recent years and recent biological findings about how oligodendrocytes mature after reactivation of their staminal niche. These data have posed novel questions and opened new views about how the adult brain is repaired after myelin injury and we will discuss how these new findings might change future drug screening campaigns for CNS regenerative drugs.

scholarly journals Modelling the Human Placental Interface In Vitro—A Review

Micromachines ◽  
2021 ◽  
Vol 12 (8) ◽  
pp. 884
Author(s):  
Marta Cherubini ◽  
Scott Erickson ◽  
Kristina Haase
Keyword(s):  
Drug Testing ◽  
Cell Types ◽  
In Vitro Models ◽  
Placental Development ◽  
Scientific Challenge ◽  
Induced Pluripotent ◽  
And Function ◽  
And Control

Acting as the primary link between mother and fetus, the placenta is involved in regulating nutrient, oxygen, and waste exchange; thus, healthy placental development is crucial for a successful pregnancy. In line with the increasing demands of the fetus, the placenta evolves throughout pregnancy, making it a particularly difficult organ to study. Research into placental development and dysfunction poses a unique scientific challenge due to ethical constraints and the differences in morphology and function that exist between species. Recently, there have been increased efforts towards generating in vitro models of the human placenta. Advancements in the differentiation of human induced pluripotent stem cells (hiPSCs), microfluidics, and bioprinting have each contributed to the development of new models, which can be designed to closely match physiological in vivo conditions. By including relevant placental cell types and control over the microenvironment, these new in vitro models promise to reveal clues to the pathogenesis of placental dysfunction and facilitate drug testing across the maternal–fetal interface. In this minireview, we aim to highlight current in vitro placental models and their applications in the study of disease and discuss future avenues for these in vitro models.

Mesenchymal control over elongating and branching morphogenesis in salivary gland development

Development ◽  
1981 ◽  
Vol 66 (1) ◽  
pp. 209-221
Author(s):  
Hiroyuki Nogawa ◽  
Takeo Mizuno
Keyword(s):  
Salivary Gland ◽  
Salivary Glands ◽  
Submaxillary Gland ◽  
Branching Morphogenesis ◽  
Mouse Submaxillary Gland ◽  
Gland Development

Recombination of the epithelium and mesenchyme between quail anterior submaxillary gland (elongating type) and quail anterior lingual or mouse submaxillary gland (branching type) was effected in vitro to clarify whether the elongating morphogenesis was directed by the epithelial or the mesenchymal component. Quail anterior submaxillary epithelium recombined with quail anterior lingual or mouse submaxillary mesenchyme came to branch. Conversely, quail anterior lingual or 12-day mouse submaxillary epithelium recombined with quail anterior submaxillary mesenchyme came to elongate, though the mesenchyme was less effective with 13-day mouse submaxillary epithelium. These results suggest that the elongating or branching morphogenesis of quail salivary glands is controlled by the mesenchyme.

scholarly journals From NAFLD to MAFLD: Aligning Translational In Vitro Research to Clinical Insights

Biomedicines ◽  
2022 ◽  
Vol 10 (1) ◽  
pp. 161
Author(s):  
Alexandra Gatzios ◽  
Matthias Rombaut ◽  
Karolien Buyl ◽  
Joery De Kock ◽  
Robim M. Rodrigues ◽  
...  
Keyword(s):  
Liver Disease ◽  
Drug Development ◽  
Fatty Liver ◽  
Fatty Liver Disease ◽  
Drug Testing ◽  
Disease Modeling ◽  
In Vitro Models ◽  
Alcoholic Fatty Liver ◽  
Short Term Exposure

Although most same-stage non-alcoholic fatty liver disease (NAFLD) patients exhibit similar histologic sequelae, the underlying mechanisms appear to be highly heterogeneous. Therefore, it was recently proposed to redefine NAFLD to metabolic dysfunction-associated fatty liver disease (MAFLD) in which other known causes of liver disease such as alcohol consumption or viral hepatitis do not need to be excluded. Revised nomenclature envisions speeding up and facilitating anti-MAFLD drug development by means of patient stratification whereby each subgroup would benefit from distinct pharmacological interventions. As human-based in vitro research fulfils an irrefutable step in drug development, action should be taken as well in this stadium of the translational path. Indeed, most established in vitro NAFLD models rely on short-term exposure to fatty acids and use lipid accumulation as a phenotypic benchmark. This general approach to a seemingly ambiguous disease such as NAFLD therefore no longer seems applicable. Human-based in vitro models that accurately reflect distinct disease subgroups of MAFLD should thus be adopted in early preclinical disease modeling and drug testing. In this review article, we outline considerations for setting up translational in vitro experiments in the MAFLD era and allude to potential strategies to implement MAFLD heterogeneity into an in vitro setting so as to better align early drug development with future clinical trial designs.

Surface Modification of PEOT/PBT Membrane with Silk Fibroin Anchoring and its Potential Application in Artificial Salivary Gland Construct

2012 ◽  
Vol 538-541 ◽  
pp. 52-59
Author(s):  
Jie Zhu ◽  
Ming Shi Li ◽  
Li Qun Wang ◽  
Xiao Lin Zhu
Keyword(s):  
Salivary Gland ◽  
Silk Fibroin ◽  
Potential Application ◽  
Contact Angles ◽  
Water Contact ◽  
Polar Groups ◽  
Poly Ethylene Oxide ◽  
Poly Ethylene ◽  
Surface Modified

We reported the preparation of surface modified poly (ethylene oxide terephthalate) - poly (butylene terephthalate) membrane by the method of silk fibroin anchoring, namely SF/(PEOT/PBT). Its surface properties were characterized by contact angles and XPS and the biocompatibility of the composite membrane was further evaluated by human salivary epithelial cells (HSG cells) growth in vitro. Results revealed that SF/(PEOT/PBT) possessed the low water contact angle (48.0±3.0°) and immobilized a great amount of fibroin (fibroin surface coverage: 26.39 wt%), which attributed to the formation of polar groups such as hydrosulfide group, sulfonic group, carboxyl and carbonyl ones in the process of SO2 plasma treatment. HSG cells growth in vitro indicated that the silk fibroin anchoring could significantly enhance the biocompatibility of PEOT/PBT membrane, which suggested the potential application of fibroin anchoring PEOT/PBT for clinical HSG cells transplantation in the artificial salivary gland construct.

Mathematical evaluation of post-radiotherapy salivary gland function using salivary gland scintigraphy

2021 ◽  
Author(s):  
Tomohiro Itonaga ◽  
Koichi Tokuuye ◽  
Ryuji Mikami ◽  
Akira Shimizu ◽  
Hiroki Sato ◽  
...  
Keyword(s):  
Salivary Gland ◽  
Salivary Glands ◽  
Conformal Radiotherapy ◽  
Head And Neck Carcinoma ◽  
Salivary Gland Function ◽  
Salivary Gland Scintigraphy ◽  
Radiotherapy Group ◽  
Tolerance Dose ◽  
Gland Function ◽  
Mathematical Evaluation

Objective: Xerostomia is the most common treatment-related toxicity after radiotherapy (RT) for head and neck carcinoma, reducing the quality of life of patients due to a decrease in salivary gland function. Methods: Salivary gland scintigraphy was performed to quantitatively evaluate the salivary gland functions in patients undergoing RT. It was done chronologically for 62 salivary glands of 31 patients before RT and retested 12 months later. Results: The salivary gland functions of most patients deteriorated post-RT and recovered when the radiation dose to the salivary gland was not high. The mean dose to the salivary gland was found to be the most reliable factor in deteriorating salivary gland function, and the tolerance dose was determined to be 46 Gy. The recovery rate of salivary gland function after 1 year of RT was 72% in the RT alone group (n = 10), 56% in the conformal radiotherapy group (n = 15), and 44% in the bioradiotherapy group (n = 6). Conclusion: Scintigraphy revealed that the salivary glands recovered from post-RT hypofunction when decreased doses were administered. The determined tolerance dose of 46 Gy may guide the approach to minimizing associated xerostomia in RT. Advances in knowledge: In this study, the average tolerated dose to the salivary glands was 46 Gy.

Salivary gland diseases

2018 ◽  
Author(s):  
Max Robinson ◽  
Keith Hunter ◽  
Michael Pemberton ◽  
Philip Sloan
Keyword(s):  
Salivary Gland ◽  
Salivary Glands ◽  
Submandibular Gland ◽  
Neck Region ◽  
Normal Function ◽  
Minor Salivary Glands ◽  
Flow Rates ◽  
Endocrine Disturbances ◽  
Systemic Factors ◽  
Gland Function

The salivary glands consist of three paired major glands—parotid, sub­mandibular, and sublingual—and the countless minor salivary glands found in almost every part of the oral cavity, except the gingiva and anterior regions of the hard palate. The secretion of saliva is essential for the normal function and health of the mouth, and disorders of salivary gland function predispose to oral disease. Functional disorders in salivary secretion may be associated with primary salivary gland disease but in other cases are a consequence of systemic factors, such as medi­cations, endocrine disturbances, and neurological disease, which are discussed in Chapter 10. Developmental anomalies of the salivary glands are rare. Aplasia of one or more major glands and atresia of one or more major salivary gland ducts have been reported. Congenital aplasia of the parotid gland may be associated with other facial abnormalities, e.g. ectodermal dysplasia, mandibulofacial dysostosis, and hemifacial microsomia. Heterotopic salivary tissue has been reported from a variety of sites in the head and neck region, the most frequent being its inclusion at the angle, or within the body, of the mandible, called a Stafne bone cavity. It is usually an incidental radiological finding and appears as a round or oval, well-demarcated radiolucency between the premolar region and angle of the jaw, and is typically located beneath the inferior dental canal. The radiographic appearances are due to a saucer-shaped depression or concavity of varying depth on the lingual aspect of the mandible, which contains salivary tissue in continuity with the submandibular gland. Accessory parotid tissue within the cheek or masseter muscle is rela­tively common and is subject to the same diseases that may affect the main gland. Age changes can be detected in both major and minor salivary glands. Reduction in the weights of submandibular and parotid glands has been reported with increasing age, associated in the submandibular gland with an age-dependent reduction in flow rates. By contrast, sev­eral studies have demonstrated that there is no significant reduction in parotid flow rates in the elderly.

scholarly journals Natriuretic peptide system expression in murine and human submandibular salivary glands: a study of the spatial localisation of ANB, BNP, CNP and their receptors

2019 ◽  
Vol 51 (1) ◽  
pp. 3-13
Author(s):  
Araz Ahmed ◽  
Alessandro Gulino ◽  
Simita Amayo ◽  
Walter Arancio ◽  
Ada Maria Florena ◽  
...  
Keyword(s):  
Salivary Gland ◽  
Salivary Glands ◽  
Natriuretic Peptide ◽  
Autonomic Nerves ◽  
Submandibular Salivary Glands ◽  
Peptide System ◽  
Glandular Structures ◽  
Gland Function ◽  
Autocrine Signalling ◽  
Natriuretic Peptide System

Abstract The natriuretic peptide (NP) system comprises of three ligands, the Atrial Natriuretic Peptide (ANP), Brain Natriuretic peptide (BNP) and C-type Natriuretic peptide (CNP), and three natriuretic peptide receptors, NPRA, NPRB and NPRC. Here we present a comprehensive study of the natriuretic peptide system in healthy murine and human submandibular salivary glands (SMGs). We show CNP is the dominant NP in mouse and human SMG and is expressed together with NP receptors in ducts, autonomic nerves and the microvasculature of the gland, suggesting CNP autocrine signalling may take place in some of these glandular structures. These data suggest the NP system may control salivary gland function during homeostasis through the regulation of electrolyte re-absorption, neural stimulation and/or blood vessel wall contraction/relaxation. We also show abnormal expression of NPRA in the stroma of a subset of human SMGs resected from patients diagnosed with oral squamous cell carcinoma (OSCC) of non-salivary gland origin. This finding warrants further research to investigate a possible correlation between early OSCC invasion and NPRA overexpression.

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