Multi-compartment Organ-on-a-Chip Based on Electrospun Nanofiber Membrane as In Vitro Jaundice Disease Model

2021 ◽  
Author(s):  
Fan Lei ◽  
Minhua Liang ◽  
Yang Liu ◽  
Hanhao Huang ◽  
Haofei Li ◽  
...  
Keyword(s):  
Disease Model ◽  
Electrospun Nanofiber ◽  
Nanofiber Membrane ◽  
Organ On A Chip

scholarly journals On Stabilization of PVPA/PVA Electrospun Nanofiber Membrane and Its Effect on Material Properties and Biocompatibility

2012 ◽  
Vol 2012 ◽  
pp. 1-9 ◽  
Author(s):  
Rose Ann Franco ◽  
Young-Ki Min ◽  
Hun-Mo Yang ◽  
Byong-Taek Lee
Keyword(s):  
Material Properties ◽  
Membrane Surface ◽  
Biological Response ◽  
Chemical Crosslinking ◽  
Electrospun Nanofiber ◽  
Nanofiber Membrane ◽  
Visual Examination ◽  
Physical Treatment ◽  
Heat Treated

A novel nanofiber membrane was fabricated by electrospinning composed of polyvinyl phosphonic acid (PVPA) and polyvinyl alcohol (PVA). Stabilization was done due to the high dissolvability of the membrane when in contact with water. Physical treatment was done by exposure to heat at 150°C in a vacuum environment at different periods of time. Chemical crosslinking was done by immersion in methanol and methanol/ glutaraldehyde. A heat-exposed membrane was also further crosslinked chemically. All conditions were compared with regards to its effect on the material properties of the membranes and its biological responsein vitrowith MG-63 osteoblast-like cell line. Visual examination and dimensional analyses showed that heat treatment produced discoloration on the membrane surface and chemical crosslinking reduced membrane dimensions. Tensile strength and strain improved in crosslinked membranes compared to noncrosslinked counterpart. Swelling and degradation was also investigated and was seen to vary depending on the crosslinking condition. Biocompatibility was observed to be more favorable in heat-treated membranes.

scholarly journals Rapid target validation in a Cas9-inducible hiPSC derived kidney model

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Yasaman Shamshirgaran ◽  
Anna Jonebring ◽  
Anna Svensson ◽  
Isabelle Leefa ◽  
Mohammad Bohlooly-Y ◽  
...  
Keyword(s):  
High Efficiency ◽  
Disease Modeling ◽  
Genetic Manipulation ◽  
Disease Model ◽  
Genetically Engineered ◽  
Model Systems ◽  
Target Validation ◽  
Direct Differentiation ◽  
Kidney Organoids

AbstractRecent advances in induced pluripotent stem cells (iPSCs), genome editing technologies and 3D organoid model systems highlight opportunities to develop new in vitro human disease models to serve drug discovery programs. An ideal disease model would accurately recapitulate the relevant disease phenotype and provide a scalable platform for drug and genetic screening studies. Kidney organoids offer a high cellular complexity that may provide greater insights than conventional single-cell type cell culture models. However, genetic manipulation of the kidney organoids requires prior generation of genetically modified clonal lines, which is a time and labor consuming procedure. Here, we present a methodology for direct differentiation of the CRISPR-targeted cell pools, using a doxycycline-inducible Cas9 expressing hiPSC line for high efficiency editing to eliminate the laborious clonal line generation steps. We demonstrate the versatile use of genetically engineered kidney organoids by targeting the autosomal dominant polycystic kidney disease (ADPKD) genes: PKD1 and PKD2. Direct differentiation of the respective knockout pool populations into kidney organoids resulted in the formation of cyst-like structures in the tubular compartment. Our findings demonstrated that we can achieve > 80% editing efficiency in the iPSC pool population which resulted in a reliable 3D organoid model of ADPKD. The described methodology may provide a platform for rapid target validation in the context of disease modeling.

scholarly journals Arrayed CRISPR reveals genetic regulators of tau aggregation, autophagy and mitochondria in Alzheimer’s disease model

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Lishu Duan ◽  
Mufeng Hu ◽  
Joseph A. Tamm ◽  
Yelena Y. Grinberg ◽  
Fang Shen ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Drug Discovery ◽  
Disease Model ◽  
Mitochondrial Morphology ◽  
Individual Gene ◽  
Human Genes ◽  
Future Drug ◽  
Tau Aggregation

AbstractAlzheimer’s disease (AD) is a common neurodegenerative disease with poor prognosis. New options for drug discovery targets are needed. We developed an imaging based arrayed CRISPR method to interrogate the human genome for modulation of in vitro correlates of AD features, and used this to assess 1525 human genes related to tau aggregation, autophagy and mitochondria. This work revealed (I) a network of tau aggregation modulators including the NF-κB pathway and inflammatory signaling, (II) a correlation between mitochondrial morphology, respiratory function and transcriptomics, (III) machine learning predicted novel roles of genes and pathways in autophagic processes and (IV) individual gene function inferences and interactions among biological processes via multi-feature clustering. These studies provide a platform to interrogate underexplored aspects of AD biology and offer several specific hypotheses for future drug discovery efforts.

scholarly journals Mechanical Strain-Enabled Reconstitution of Dynamic Environment in Organ-on-a-Chip Platforms: A Review

Micromachines ◽  
2021 ◽  
Vol 12 (7) ◽  
pp. 765
Author(s):  
Qianbin Zhao ◽  
Tim Cole ◽  
Yuxin Zhang ◽  
Shi-Yang Tang
Keyword(s):  
Cell Culture ◽  
Shear Stress ◽  
Cultured Cells ◽  
Mechanical Strain ◽  
3D Cell Culture ◽  
Small Scale ◽  
Mechanical Stimuli ◽  
Human Organ ◽  
Organ On A Chip

Organ-on-a-chip (OOC) uses the microfluidic 3D cell culture principle to reproduce organ- or tissue-level functionality at a small scale instead of replicating the entire human organ. This provides an alternative to animal models for drug development and environmental toxicology screening. In addition to the biomimetic 3D microarchitecture and cell–cell interactions, it has been demonstrated that mechanical stimuli such as shear stress and mechanical strain significantly influence cell behavior and their response to pharmaceuticals. Microfluidics is capable of precisely manipulating the fluid of a microenvironment within a 3D cell culture platform. As a result, many OOC prototypes leverage microfluidic technology to reproduce the mechanically dynamic microenvironment on-chip and achieve enhanced in vitro functional organ models. Unlike shear stress that can be readily generated and precisely controlled using commercial pumping systems, dynamic systems for generating proper levels of mechanical strains are more complicated, and often require miniaturization and specialized designs. As such, this review proposes to summarize innovative microfluidic OOC platforms utilizing mechanical actuators that induce deflection of cultured cells/tissues for replicating the dynamic microenvironment of human organs.

scholarly journals Cytokinin Plant Hormones Have Neuroprotective Activity in In Vitro Models of Parkinson’s Disease

Molecules ◽  
2021 ◽  
Vol 26 (2) ◽  
pp. 361
Author(s):  
Gabriel Gonzalez ◽  
Jiří Grúz ◽  
Cosimo Walter D’Acunto ◽  
Petr Kaňovský ◽  
Miroslav Strnad
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Cell Death ◽  
Neuronal Cell Death ◽  
Disease Model ◽  
Neuronal Cell ◽  
Zeatin Riboside ◽  
Neuroprotective Activity ◽  
Protective Activity

Cytokinins are adenine-based phytohormones that regulate key processes in plants, such as cell division and differentiation, root and shoot growth, apical dominance, branching, and seed germination. In preliminary studies, they have also shown protective activities against human neurodegenerative diseases. To extend knowledge of the protection (protective activity) they offer, we investigated activities of natural cytokinins against salsolinol (SAL)-induced toxicity (a Parkinson’s disease model) and glutamate (Glu)-induced death of neuron-like dopaminergic SH-SY5Y cells. We found that kinetin-3-glucoside, cis-zeatin riboside, and N6-isopentenyladenosine were active in the SAL-induced PD model. In addition, trans-, cis-zeatin, and kinetin along with the iron chelator deferoxamine (DFO) and the necroptosis inhibitor necrostatin 1 (NEC-1) significantly reduced cell death rates in the Glu-induced model. Lactate dehydrogenase assays revealed that the cytokinins provided lower neuroprotective activity than DFO and NEC-1. Moreover, they reduced apoptotic caspase-3/7 activities less strongly than DFO. However, the cytokinins had very similar effects to DFO and NEC-1 on superoxide radical production. Overall, they showed protective activity in the SAL-induced model of parkinsonian neuronal cell death and Glu-induced model of oxidative damage mainly by reduction of oxidative stress.

scholarly journals Dual Role of Interleukin-10 in Murine NZB/W F1 Lupus

2021 ◽  
Vol 22 (3) ◽  
pp. 1347
Author(s):  
Anaïs Amend ◽  
Natalie Wickli ◽  
Anna-Lena Schäfer ◽  
Dalina T. L. Sprenger ◽  
Rudolf A. Manz ◽  
...  
Keyword(s):  
B Cell ◽  
Disease Model ◽  
Interleukin 10 ◽  
Immune Functions ◽  
Murine Lupus ◽  
Anti Inflammatory ◽  
In Vivo Effects

As a key anti-inflammatory cytokine, IL-10 is crucial in preventing inflammatory and autoimmune diseases. However, in human and murine lupus, its role remains controversial. Our aim was to understand regulation and immunologic effects of IL-10 on different immune functions in the setting of lupus. This was explored in lupus-prone NZB/W F1 mice in vitro and vivo to understand IL-10 effects on individual immune cells as well as in the complex in vivo setting. We found pleiotropic IL-10 expression that largely increased with progressing lupus, while IL-10 receptor (IL-10R) levels remained relatively stable. In vitro experiments revealed pro- and anti-inflammatory IL-10 effects. Particularly, IL-10 decreased pro-inflammatory cytokines and slowed B cell proliferation, thereby triggering plasma cell differentiation. The frequent co-expression of ICOS, IL-21 and cMAF suggests that IL-10-producing CD4 T cells are important B cell helpers in this context. In vitro and in vivo effects of IL-10 were not fully concordant. In vivo IL-10R blockade slightly accelerated clinical lupus manifestations and immune dysregulation. Altogether, our side-by-side in vitro and in vivo comparison of the influence of IL-10 on different aspects of immunity shows that IL-10 has dual effects. Our results further reveal that the overall outcome may depend on the interplay of different factors such as target cell, inflammatory and stimulatory microenvironment, disease model and state. A comprehensive understanding of such influences is important to exploit IL-10 as a therapeutic target.

scholarly journals O4: A NOVEL BOWEL DISEASE MODEL: PHENOTYPIC DIVERSITY OF CONTROL VS FAP ORGANOIDS

2021 ◽  
Vol 108 (Supplement_1) ◽  
Author(s):  
I Martin ◽  
Y Wu ◽  
R Patel ◽  
P Kalra ◽  
S Clark K ◽  
...  
Keyword(s):  
Familial Adenomatous Polyposis ◽  
Phenotypic Diversity ◽  
Disease Model ◽  
Duodenal Mucosa ◽  
In Vitro Models ◽  
Upper Gastrointestinal Endoscopy ◽  
Adenomatous Polyposis ◽  
Ki 67 ◽  
Ring Structures

Abstract Introduction The lifetime risk of colorectal cancer in familial adenomatous polyposis (FAP) approaches 100%. In patients who have undergone prophylactic colectomy, duodenal cancer is 100-300 times more common than in the general population, and an important cause of death. We aimed to develop in vitro models of mucosal crypt-derived organoids from patients with FAP. Method Biopsies from apparent healthy duodenal mucosa of FAP patients undergoing upper gastrointestinal endoscopy or surgery yielded crypts that were immobilised in Matrigel Basement Membrane Matrix (Corning) and cultured in IntestiCult Organoid Growth Medium (StemCell Technologies) to generate organoids for further morphologic and immunocytochemistry analyses (Dako and Abcam antibodies). Result Duodenal crypt-derived organoids from one healthy volunteer formed ring structures (days 1 -2) that progressed to expected branched structures (days 4-7). FAP-derived organoids from 9 patients all generated organoids with aberrant morphologies. These organoids expressed markers of Paneth cells (lysozyme), proliferation (Ki-67), goblet cells (Muc-2) and the single cell layer of mucosal epithelium (CK18). Conclusion This is the first report of duodenal crypt-derived organoids generated from FAP patients. Aberrant organoid morphologies were observed in all 9 patients. Immunocytochemistry confirmed markers of duodenal epithelium, suggesting a promising in vitro model to study disease aetiology in FAP. Take-home message This is a step towards a personalised model of disease for patients with familial adenomatous polyposis.

scholarly journals A σ28-Regulated Nonflagella Gene Contributes to Virulence of Campylobacter jejuni 81-176

2006 ◽  
Vol 74 (1) ◽  
pp. 769-772 ◽  
Author(s):  
Scarlett Goon ◽  
Cheryl P. Ewing ◽  
Maria Lorenzo ◽  
Dawn Pattarini ◽  
Gary Majam ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Campylobacter Jejuni ◽  
Diarrheal Disease ◽  
Intestinal Epithelial Cells ◽  
Disease Model ◽  
Intestinal Epithelial ◽  
Model Expression

ABSTRACT A Campylobacter jejuni 81-176 mutant in Cj0977 was fully motile but reduced >3 logs compared to the parent in invasion of intestinal epithelial cells in vitro. The mutant was also attenuated in a ferret diarrheal disease model. Expression of Cj0977 protein was dependent on a minimal flagella structure.

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