Induced pluripotent stem cell-based organ-on-a-chip as personalized drug screening tools: A focus on neurodegenerative disorders

Fanizza, Francesca; Campanile, Marzia; Forloni, Gianluigi; Giordano, Carmen; Albani, Diego

doi:10.1177/20417314221095339

Cited by 26 publications

(14 citation statements)

References 156 publications

(240 reference statements)

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“…Therefore, organoid-on-a-chip platform has been studied with microfluidic devices loaded with organoids. 114 – 116 This innovative platform can induce vascularization of organoids through the fluidic shear stress and pre-vascular network within chip, thereby enhancing organoid growth and inhibiting the apoptosis of cells inside the organoids. 117 – 119 Furthermore, it can compartmentalize different types of organoids to investigate multi-organ interactions.…”

Section: Advanced Organoid Culture Platformsmentioning

confidence: 99%

Advanced lung organoids for respiratory system and pulmonary disease modeling

Joo,

Min,

Cho

2024

J Tissue Eng

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Amidst the recent coronavirus disease 2019 (COVID-19) pandemic, respiratory system research has made remarkable progress, particularly focusing on infectious diseases. Lung organoid, a miniaturized structure recapitulating lung tissue, has gained global attention because of its advantages over other conventional models such as two-dimensional (2D) cell models and animal models. Nevertheless, lung organoids still face limitations concerning heterogeneity, complexity, and maturity compared to the native lung tissue. To address these limitations, researchers have employed co-culture methods with various cell types including endothelial cells, mesenchymal cells, and immune cells, and incorporated bioengineering platforms such as air-liquid interfaces, microfluidic chips, and functional hydrogels. These advancements have facilitated applications of lung organoids to studies of pulmonary diseases, providing insights into disease mechanisms and potential treatments. This review introduces recent progress in the production methods of lung organoids, strategies for improving maturity, functionality, and complexity of organoids, and their application in disease modeling, including respiratory infection and pulmonary fibrosis.

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Section: Advanced Organoid Culture Platformsmentioning

confidence: 99%

Advanced lung organoids for respiratory system and pulmonary disease modeling

Joo,

Min,

Cho

2024

J Tissue Eng

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“…[157,158]. Thanks to the combination of computerized 3D bioprinting using microfluidic systems designed with the incorporation of living cells, organs-on-chips can allow structural resemblance at both physiological and pathophysiological levels [12,[159][160][161]. The system can also be automated, requires a very low amount of culture medium, and can be designed to image cells in real time by confocal microscopy.…”

Section: Organs-on-chipsmentioning

confidence: 99%

In Vitro 3D Modeling of Neurodegenerative Diseases

Louit

Galbraith²,

Berthod³

2023

Bioengineering

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The study of neurodegenerative diseases (such as Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, or amyotrophic lateral sclerosis) is very complex due to the difficulty in investigating the cellular dynamics within nervous tissue. Despite numerous advances in the in vivo study of these diseases, the use of in vitro analyses is proving to be a valuable tool to better understand the mechanisms implicated in these diseases. Although neural cells remain difficult to obtain from patient tissues, access to induced multipotent stem cell production now makes it possible to generate virtually all neural cells involved in these diseases (from neurons to glial cells). Many original 3D culture model approaches are currently being developed (using these different cell types together) to closely mimic degenerative nervous tissue environments. The aim of these approaches is to allow an interaction between glial cells and neurons, which reproduces pathophysiological reality by co-culturing them in structures that recapitulate embryonic development or facilitate axonal migration, local molecule exchange, and myelination (to name a few). This review details the advantages and disadvantages of techniques using scaffolds, spheroids, organoids, 3D bioprinting, microfluidic systems, and organ-on-a-chip strategies to model neurodegenerative diseases.

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“…4 Moreover, the connection of multiple OoC devices into body-on-a-chip platforms allows the preliminary analysis of organ cross-talks and integrated responses to drug administration. 6 The cultivation of differentiated induced pluripotent stem cells (iPSCs) into the OoC provides a valuable tool to develop patient-specific drug screening models, having also the potential to better predict side effects and thus contributing to reduce the percentage of drug failure in clinical trials, 7 also in a personalized medicine perspective. Drug-induced liver injury is an adverse event that frequently leads to drug failure in trials and withdrawal from the market.…”

Section: ■ Introductionmentioning

confidence: 99%

Development of an Induced Pluripotent Stem Cell-Based Liver-on-a-Chip Assessed with an Alzheimer’s Disease Drug

Fanizza

Boeri

Donnaloja

et al. 2023

ACS Biomater. Sci. Eng.

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Liver-related drug metabolism is a key aspect of pharmacokinetics and possible toxicity. From this perspective, the availability of advanced in vitro models for drug testing is still an open need, also to the end of reducing the burden of in vivo experiments. In this scenario, organ-on-a-chip is gaining attention as it couples a state-of-the art in vitro approach to the recapitulation of key in vivo physiological features such as fluidodynamics and a tri-dimensional cytoarchitecture. We implemented a novel liver-on-a-chip (LoC) device based on an innovative dynamic device (MINERVA 2.0) where functional hepatocytes (iHep) have been encapsulated into a 3D hydrogel matrix interfaced through a porous membrane with endothelial cells (iEndo)]. Both lines were derived from human-induced pluripotent stem cells (iPSCs), and the LoC was functionally assessed with donepezil, a drug approved for Alzheimer’s disease therapy. The presence of iEndo and a 3D microenvironment enhanced the expression of liver-specific physiologic functions as in iHep, after 7 day perfusion, we noticed an increase of albumin, urea production, and cytochrome CYP3A4 expression compared to the iHep static culture. In particular, for donepezil kinetics, a computational fluid dynamic study conducted to assess the amount of donepezil diffused into the LoC indicated that the molecule should be able to pass through the iEndo and reach the target iHep construct. Then, we performed experiments of donepezil kinetics that confirmed the numerical simulations. Overall, our iPSC-based LoC reproduced the in vivo physiological microenvironment of the liver and was suitable for potential hepatotoxic screening studies.

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Induced pluripotent stem cell-based organ-on-a-chip as personalized drug screening tools: A focus on neurodegenerative disorders

Cited by 26 publications

References 156 publications

Advanced lung organoids for respiratory system and pulmonary disease modeling

Advanced lung organoids for respiratory system and pulmonary disease modeling

In Vitro 3D Modeling of Neurodegenerative Diseases

Development of an Induced Pluripotent Stem Cell-Based Liver-on-a-Chip Assessed with an Alzheimer’s Disease Drug

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