scholarly journals Latest Trends in Biosensing for Microphysiological Organs-on-a-Chip and Body-on-a-Chip Systems

Biosensors ◽  
2019 ◽  
Vol 9 (3) ◽  
pp. 110 ◽  
Author(s):  
Sebastian Kratz ◽  
Gregor Höll ◽  
Patrick Schuller ◽  
Peter Ertl ◽  
Mario Rothbauer
Keyword(s):  
Animal Testing ◽  
Human Organ ◽  
Organ Specific ◽  
Vitro Model ◽  
Induced Pluripotent ◽  
Organ Models ◽  
Specific Reactions ◽  
Analysis Platform

Organs-on-chips are considered next generation in vitro tools capable of recreating in vivo like, physiological-relevant microenvironments needed to cultivate 3D tissue-engineered constructs (e.g., hydrogel-based organoids and spheroids) as well as tissue barriers. These microphysiological systems are ideally suited to (a) reduce animal testing by generating human organ models, (b) facilitate drug development and (c) perform personalized medicine by integrating patient-derived cells and patient-derived induced pluripotent stem cells (iPSCs) into microfluidic devices. An important aspect of any diagnostic device and cell analysis platform, however, is the integration and application of a variety of sensing strategies to provide reliable, high-content information on the health status of the in vitro model of choice. To overcome the analytical limitations of organs-on-a-chip systems a variety of biosensors have been integrated to provide continuous data on organ-specific reactions and dynamic tissue responses. Here, we review the latest trends in biosensors fit for monitoring human physiology in organs-on-a-chip systems including optical and electrochemical biosensors.

Human Microphysiological Models of Airway and Alveolar Epithelium

2021 ◽  
Author(s):  
Dave Anuj Lagowala ◽  
Seoyoung Kwon ◽  
Venkataramana K. Sidhaye ◽  
Deok-Ho Kim
Keyword(s):  
Respiratory Disease ◽  
Cell Biology ◽  
Disease Modeling ◽  
Alveolar Epithelium ◽  
Animal Testing ◽  
Future Directions ◽  
Human Organ ◽  
Organ Specific

Human organ-on-a-chip models are powerful tools for pre-clinical research that can be used to study the mechanisms of disease and evaluate new targets for therapeutic intervention. Lung-on-a-chip models have been one of the most well-characterized designs in this field, and can be altered to evaluate various types of respiratory disease and to assess treatment candidates prior to clinical testing. These systems are capable of overcoming the flaws of conventional 2D cell culture and in vivo animal testing due to their ability to accurately recapitulate the in vivo microenvironment of human tissue with tunable material properties, microfluidic integration, delivery of precise mechanical and biochemical cues, and designs with organ-specific architecture. In this review, we first describe an overview of currently available lung-on-a-chip designs. We then present how recent innovations in human stem cell biology, tissue engineering, and microfabrication can be used to create more predictive human lung-on-a-chip models for studying respiratory disease. Finally, we discuss the current challenges and future directions of lung-on-a-chip designs for in vitro disease modeling with particular focus on immune and multi-organ interactions.

scholarly journals Teaching and training in substitutive approaches to animal testing: Commitment of the University of Genoa

2020 ◽  
Author(s):  
Anna Maria Bassi
Keyword(s):  
Work Experience ◽  
Ethical Issues ◽  
Animal Testing ◽  
Vitro Model ◽  
Teaching Programs ◽  
The University ◽  
Graduating Students ◽  
And Training

The 21st century life science requires that scientists become aware of scientific and ethical issues of substitutive approaches to animal testing. For more than 20 years Dr Bassi Team at University of Genoa promotes several activities in Academia on the Replacement of Animal Testing: 2 days training course, lectures within teaching programs, work experience opportunities for graduated or graduating students, stages for Biology, Medicine and Surgery degrees and PhD courses on human in vitro model disease projects, This effort is now improved by Centro3R activities to increase the number of scientists aware of effective alternatives to classical in vivo approaches, and prevent needless suffering of animals.

scholarly journals Human Organ-Specific 3D Cancer Models Produced by the Stromal Self-Assembly Method of Tissue Engineering for the Study of Solid Tumors

2020 ◽  
Vol 2020 ◽  
pp. 1-23 ◽  
Author(s):  
Vincent Roy ◽  
Brice Magne ◽  
Maude Vaillancourt-Audet ◽  
Mathieu Blais ◽  
Stéphane Chabaud ◽  
...  
Keyword(s):  
Tissue Engineering ◽  
Tumor Microenvironment ◽  
Self Assembly ◽  
The Self ◽  
Human Organ ◽  
Assembly Method ◽  
Cancer Models ◽  
Organ Specific

Cancer research has considerably progressed with the improvement of in vitro study models, helping to understand the key role of the tumor microenvironment in cancer development and progression. Over the last few years, complex 3D human cell culture systems have gained much popularity over in vivo models, as they accurately mimic the tumor microenvironment and allow high-throughput drug screening. Of particular interest, in vitrohuman 3D tissue constructs, produced by the self-assembly method of tissue engineering, have been successfully used to model the tumor microenvironment and now represent a very promising approach to further develop diverse cancer models. In this review, we describe the importance of the tumor microenvironment and present the existing in vitro cancer models generated through the self-assembly method of tissue engineering. Lastly, we highlight the relevance of this approach to mimic various and complex tumors, including basal cell carcinoma, cutaneous neurofibroma, skin melanoma, bladder cancer, and uveal melanoma.

Human Postnatal Mesenchymalstem Cell Derived Islets as a Model for Diabetes Research

2020 ◽  
Vol 17 ◽  
Author(s):  
Avinash Kharat ◽  
Bhawna Chadravanshi ◽  
Avinash Sanap ◽  
Supriya Kheur ◽  
Ramesh Bhonde
Keyword(s):  
Stem Cells ◽  
Drug Screening ◽  
Diabetes Research ◽  
Animal Testing ◽  
Patients With Diabetes ◽  
Glucose Challenge ◽  
Vitro Model ◽  
Novel Drug

Background:: The scarcity of human cadaver islets for transplantation in patients with Diabetes Mellitus (DM) has necessitated the search for alternative islet sources. With advancing islet biology research, islet-like clusters (ILCs) derived from stem cells have demonstrated potential for treating DM and in novel drug discovery programs for drug and cytotoxicity testing. -: In vitro differentiation of ILCs from stem cells also provides an opportunity to mimic the in vivo islet developmental pathways. In vitro derived ILCs are often considered immature,as they do not respond to glucose challenge efficiently. However, the in vitro and in vivo performance of ILCs can be imroved by pharmacological preconditioning. Methods:: In this review, we discuss how ILCs generated from human postnatal tissues can be utilized as an in-vitro model to study cytotoxicity, drug screening and enhancement of transplantation efficacy. Use of human cadevar islets is not permitted for research purposes in India. Under these restrictions, the application of ILCs in drug screening and their role in complementing, reducing, and replacing animal testing will evolve a reliable platform in vitro screening as well as for stem cell-based treatment in DM.

scholarly journals In vitro monitoring of HTR2A-positive neurons derived from human-induced pluripotent stem cells

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Kento Nakai ◽  
Takahiro Shiga ◽  
Rika Yasuhara ◽  
Avijite Kumer Sarkar ◽  
Yuka Abe ◽  
...  
Keyword(s):  
Stem Cells ◽  
Induced Pluripotent Stem Cells ◽  
Pluripotent Stem Cells ◽  
Neurological Diseases ◽  
Electrophysiological Properties ◽  
Maturation Stages ◽  
Vitro Model ◽  
Induced Pluripotent

AbstractThe serotonin 5-HT2A receptor (5-HT2AR) has been receiving increasing attention because its genetic variants have been associated with a variety of neurological diseases. To elucidate the pathogenesis of the neurological diseases associated with 5-HT2AR gene (HTR2A) variants, we have previously established a protocol to induce HTR2A-expressing neurons from human-induced pluripotent stem cells (hiPSCs). Here, we investigated the maturation stages and electrophysiological properties of HTR2A-positive neurons induced from hiPSCs and constructed an HTR2A promoter-specific reporter lentivirus to label the neurons. We found that neuronal maturity increased over time and that HTR2A expression was induced at the late stage of neuronal maturation. Furthermore, we demonstrated successful labelling of the HTR2A-positive neurons, which had fluorescence and generated repetitive action potentials in response to depolarizing currents and an inward current during the application of TCB-2, a selective agonist of 5-HT2ARs, respectively. These results indicated that our in vitro model mimicked the in vivo dynamics of 5-HT2AR. Therefore, in vitro monitoring of the function of HTR2A-positive neurons induced from hiPSCs could help elucidate the pathophysiological mechanisms of neurological diseases associated with genetic variations of the HTR2A gene.

scholarly journals Functional and Transcriptional Adaptations of Blood Monocytes Recruited to the Cystic Fibrosis Airway Microenvironment In Vitro

2021 ◽  
Vol 22 (5) ◽  
pp. 2530
Author(s):  
Bijean D. Ford ◽  
Diego Moncada Giraldo ◽  
Camilla Margaroli ◽  
Vincent D. Giacalone ◽  
Milton R. Brown ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Bactericidal Activity ◽  
Scavenger Receptor ◽  
Receptor Expression ◽  
Blood Monocytes ◽  
Bacterial Killing ◽  
Blood Neutrophils ◽  
Vitro Model

Cystic fibrosis (CF) lung disease is dominated by the recruitment of myeloid cells (neutrophils and monocytes) from the blood which fail to clear the lung of colonizing microbes. In prior in vitro studies, we showed that blood neutrophils migrated through the well-differentiated lung epithelium into the CF airway fluid supernatant (ASN) mimic the dysfunction of CF airway neutrophils in vivo, including decreased bactericidal activity despite an increased metabolism. Here, we hypothesized that, in a similar manner to neutrophils, blood monocytes undergo significant adaptations upon recruitment to CFASN. To test this hypothesis, primary human blood monocytes were transmigrated in our in vitro model into the ASN from healthy control (HC) or CF subjects to mimic in vivo recruitment to normal or CF airways, respectively. Surface phenotype, metabolic and bacterial killing activities, and transcriptomic profile by RNA sequencing were quantified post-transmigration. Unlike neutrophils, monocytes were not metabolically activated, nor did they show broad differences in activation and scavenger receptor expression upon recruitment to the CFASN compared to HCASN. However, monocytes recruited to CFASN showed decreased bactericidal activity. RNASeq analysis showed strong effects of transmigration on monocyte RNA profile, with differences between CFASN and HCASN conditions, notably in immune signaling, including lower expression in the former of the antimicrobial factor ISG15, defensin-like chemokine CXCL11, and nitric oxide-producing enzyme NOS3. While monocytes undergo qualitatively different adaptations from those seen in neutrophils upon recruitment to the CF airway microenvironment, their bactericidal activity is also dysregulated, which could explain why they also fail to protect CF airways from infection.

scholarly journals Radiofrequency Irradiation Modulates TRPV1-Related Burning Sensation in Rosacea

Molecules ◽  
2021 ◽  
Vol 26 (5) ◽  
pp. 1424
Author(s):  
Seyeon Oh ◽  
Myeongjoo Son ◽  
Joonhong Park ◽  
Donghwan Kang ◽  
Kyunghee Byun
Keyword(s):  
Burning Sensation ◽  
In Vivo Model ◽  
Molecular Evidence ◽  
Exposed Skin ◽  
Heat Treated ◽  
Vitro Model ◽  
Effective Use ◽  
Inflammatory Molecules

Rosacea is a skin inflammatory condition that is accompanied by not only redness and flushing but also unseen symptoms, such as burning, stinging, and itching. TRPV1 expression in UVB-exposed skin can lead to a painful burning sensation. Upregulated TRPV1 expression helps release neuropeptides, including calcitonin gene-related peptide, pituitary adenylate cyclase-activating polypeptide, and vasoactive intestinal peptide, which can activate macrophage and inflammatory molecules. In this study, we found that radiofrequency (RF) irradiation reduced TRPV1 activation and neuropeptide expression in a UVB-exposed in vivo model and UVB- or heat-treated in an in vitro model. RF irradiation attenuated neuropeptide-induced macrophage activation and inflammatory molecule expression. Interestingly, the burning sensation in the skin of UVB-exposed mice and patients with rosacea was significantly decreased by RF irradiation. These results can provide experimental and molecular evidence on the effective use of RF irradiation for the burning sensation in patients with rosacea.

scholarly journals Generation of a Novel In Vitro Model to Study Endothelial Dysfunction from Atherothrombotic Specimens

2021 ◽  
Author(s):  
Susan Gallogly ◽  
Takeshi Fujisawa ◽  
John D. Hung ◽  
Mairi Brittan ◽  
Elizabeth M. Skinner ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Endothelial Dysfunction ◽  
In Vitro Model ◽  
Umbilical Vein ◽  
Coronary Syndrome ◽  
Coronary Endothelial Cells ◽  
Vitro Model ◽  
Umbilical Vein Endothelial Cells

Abstract Purpose Endothelial dysfunction is central to the pathogenesis of acute coronary syndrome. The study of diseased endothelium is very challenging due to inherent difficulties in isolating endothelial cells from the coronary vascular bed. We sought to isolate and characterise coronary endothelial cells from patients undergoing thrombectomy for myocardial infarction to develop a patient-specific in vitro model of endothelial dysfunction. Methods In a prospective cohort study, 49 patients underwent percutaneous coronary intervention with thrombus aspiration. Specimens were cultured, and coronary endothelial outgrowth (CEO) cells were isolated. CEO cells, endothelial cells isolated from peripheral blood, explanted coronary arteries, and umbilical veins were phenotyped and assessed functionally in vitro and in vivo. Results CEO cells were obtained from 27/37 (73%) atherothrombotic specimens and gave rise to cells with cobblestone morphology expressing CD146 (94 ± 6%), CD31 (87 ± 14%), and von Willebrand factor (100 ± 1%). Proliferation of CEO cells was impaired compared to both coronary artery and umbilical vein endothelial cells (population doubling time, 2.5 ± 1.0 versus 1.6 ± 0.3 and 1.2 ± 0.3 days, respectively). Cell migration was also reduced compared to umbilical vein endothelial cells (29 ± 20% versus 85±19%). Importantly, unlike control endothelial cells, dysfunctional CEO cells did not incorporate into new vessels or promote angiogenesis in vivo. Conclusions CEO cells can be reliably isolated and cultured from thrombectomy specimens in patients with acute coronary syndrome. Compared to controls, patient-derived coronary endothelial cells had impaired capacity to proliferate, migrate, and contribute to angiogenesis. CEO cells could be used to identify novel therapeutic targets to enhance endothelial function and prevent acute coronary syndromes.

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