scholarly journals Beating organs-on-chip as technological platforms in drug screening: Advanced in vitro models of human physiology and pathology

2021 ◽  
Vol 4 (s1) ◽  
Author(s):  
Paola Occhetta ◽  
Roberta Visone ◽  
Stefano Piazza ◽  
Ferran Lozano ◽  
Marco Rasponi

Taking advantages of uBeat® technology, 3D beating Organs-on-Chip integrates the native complexity of human mechanical microenvironment into clinically relevant in vitro models of human organs and diseases.

Biosensors ◽  
2020 ◽  
Vol 10 (9) ◽  
pp. 110 ◽  
Author(s):  
Erika Ferrari ◽  
Cecilia Palma ◽  
Simone Vesentini ◽  
Paola Occhetta ◽  
Marco Rasponi

Organs-on-chip (OoC), often referred to as microphysiological systems (MPS), are advanced in vitro tools able to replicate essential functions of human organs. Owing to their unprecedented ability to recapitulate key features of the native cellular environments, they represent promising tools for tissue engineering and drug screening applications. The achievement of proper functionalities within OoC is crucial; to this purpose, several parameters (e.g., chemical, physical) need to be assessed. Currently, most approaches rely on off-chip analysis and imaging techniques. However, the urgent demand for continuous, noninvasive, and real-time monitoring of tissue constructs requires the direct integration of biosensors. In this review, we focus on recent strategies to miniaturize and embed biosensing systems into organs-on-chip platforms. Biosensors for monitoring biological models with metabolic activities, models with tissue barrier functions, as well as models with electromechanical properties will be described and critically evaluated. In addition, multisensor integration within multiorgan platforms will be further reviewed and discussed.


2021 ◽  
Vol 22 (6) ◽  
pp. 2891
Author(s):  
Sonia Balestri ◽  
Alice Del Giovane ◽  
Carola Sposato ◽  
Marta Ferrarelli ◽  
Antonella Ragnini-Wilson

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.


2019 ◽  
Vol 140 ◽  
pp. 68-77 ◽  
Author(s):  
Amy Cochrane ◽  
Hugo J. Albers ◽  
Robert Passier ◽  
Christine L. Mummery ◽  
Albert van den Berg ◽  
...  

Pancreatology ◽  
2016 ◽  
Vol 16 (3) ◽  
pp. S8 ◽  
Author(s):  
Hoyin Lam ◽  
Debashis Sarker ◽  
Claire Wells

2005 ◽  
Vol 31 (8) ◽  
pp. 757-768 ◽  
Author(s):  
David D. Allen ◽  
Raúl Caviedes ◽  
Ana María Cárdenas ◽  
Takeshi Shimahara ◽  
Juan Segura-Aguilar ◽  
...  

Cells ◽  
2021 ◽  
Vol 10 (11) ◽  
pp. 3183
Author(s):  
Xingchi Chen ◽  
Chang Liu ◽  
Laureana Muok ◽  
Changchun Zeng ◽  
Yan Li

The blood–brain barrier (BBB) is a vital structure for maintaining homeostasis between the blood and the brain in the central nervous system (CNS). Biomolecule exchange, ion balance, nutrition delivery, and toxic molecule prevention rely on the normal function of the BBB. The dysfunction and the dysregulation of the BBB leads to the progression of neurological disorders and neurodegeneration. Therefore, in vitro BBB models can facilitate the investigation for proper therapies. As the demand increases, it is urgent to develop a more efficient and more physiologically relevant BBB model. In this review, the development of the microfluidics platform for the applications in neuroscience is summarized. This article focuses on the characterizations of in vitro BBB models derived from human stem cells and discusses the development of various types of in vitro models. The microfluidics-based system and BBB-on-chip models should provide a better platform for high-throughput drug-screening and targeted delivery.


Cells ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 1602
Author(s):  
Tanya J. Bennet ◽  
Avineet Randhawa ◽  
Jessica Hua ◽  
Karen C. Cheung

The lungs are affected by illnesses including asthma, chronic obstructive pulmonary disease, and infections such as influenza and SARS-CoV-2. Physiologically relevant models for respiratory conditions will be essential for new drug development. The composition and structure of the lung extracellular matrix (ECM) plays a major role in the function of the lung tissue and cells. Lung-on-chip models have been developed to address some of the limitations of current two-dimensional in vitro models. In this review, we describe various ECM substitutes utilized for modeling the respiratory system. We explore the application of lung-on-chip models to the study of cigarette smoke and electronic cigarette vapor. We discuss the challenges and opportunities related to model characterization with an emphasis on in situ characterization methods, both established and emerging. We discuss how further advancements in the field, through the incorporation of interstitial cells and ECM, have the potential to provide an effective tool for interrogating lung biology and disease, especially the mechanisms that involve the interstitial elements.


2021 ◽  
Vol 12 ◽  
pp. 204173142098520
Author(s):  
Justine Creff ◽  
Laurent Malaquin ◽  
Arnaud Besson

The intestinal epithelium, the fastest renewing tissue in human, is a complex tissue hosting multiple cell types with a dynamic and multiparametric microenvironment, making it particularly challenging to recreate in vitro. Convergence of recent advances in cellular biology and microfabrication technologies have led to the development of various bioengineered systems to model and study the intestinal epithelium. Theses microfabricated in vitro models may constitute an alternative to current approaches for studying the fundamental mechanisms governing intestinal homeostasis and pathologies, as well as for in vitro drug screening and testing. Herein, we review the recent advances in bioengineered in vitro intestinal models.


Author(s):  
Antonia Last ◽  
Michelle Maurer ◽  
Alexander S Mosig ◽  
Mark S Gresnigt ◽  
Bernhard Hube

Abstract Fungal infections (mycoses) affect over a billion people per year. Approximately two million of these infections are life-threatening, especially for patients with a compromised immune system. Fungi of the genera Aspergillus, Candida, Histoplasma, and Cryptococcus are opportunistic pathogens that contribute to a substantial number of mycoses. To optimize the diagnosis and treatment of mycoses, we need to understand the complex fungal-host interplay during pathogenesis, the fungal attributes causing virulence, and how the host resists infection via immunological defenses. In vitro models can be used to mimic fungal infections of various tissues and organs and the corresponding immune responses at near-physiological conditions. Furthermore, models can include fungal interactions with the host-microbiota to mimic the in vivo situation on skin and mucosal surfaces. This article reviews currently used in vitro models of fungal infections ranging from cell monolayers to microfluidic 3D organ-on-chip (OOC) platforms. We also discuss how OOC models can expand the toolbox for investigating interactions of fungi and their human hosts in the future.


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