Stem cells, organoids, and organ-on-a-chip models for personalized in vitro drug testing

Berlo, Damiën van; Nguyen, Vivian V. T.; Gkouzioti, Vasiliki; Leineweber, Kirsten; Verhaar, Marianne C.; Balkom, Bas W. M. van

doi:10.1016/j.cotox.2021.08.006

Cited by 25 publications

(16 citation statements)

References 46 publications

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“…These models use homogeneous and characterized cells, are economic and easily replicated, lack concerns on animal testing, and provide mechanistic data which can be directly compared with the mathematical models [ 44 ]. Recent developments in in vitro screening platforms, such as the use of induced pluripotent stem cells (iPSC), iPSC-derived organoids, organ-on-a-chip, and multi-organ-on-a-chip models allow personalized testing of drug safety and efficacy [ 24 ], while keeping the complexity of the system within limits that could be effectively modeled with mechanistic models.…”

Section: Discussionmentioning

confidence: 99%

“…Here, based on the previously developed model of integrated cholesterol biosynthesis [ 18 ], we aimed to combine in a single model both statin and anti-PCSK9 therapies. The model is formulated in an in vitro context, which is an important step in testing any potential drug, especially considering recent developments in experimental cell-based models [ 24 – 28 ].…”

Section: Introductionmentioning

confidence: 99%

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A mathematical model of in vitro hepatocellular cholesterol and lipoprotein metabolism for hyperlipidemia therapy

et al. 2022

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Cardiovascular diseases associated with high cholesterol (hypercholesterolemia) and low-density lipoproteins (LDL) levels are significant contributors to total mortality in developing and developed countries. Mathematical modeling of LDL metabolism is an important step in the development of drugs for hypercholesterolemia. The aim of this work was to develop and to analyze an integrated mathematical model of cholesterol metabolism in liver cells and its interaction with two types of drugs, statins and PCSK9 inhibitors. The model consisted of 21 ordinary differential equations (ODE) describing cholesterol biosynthesis and lipoprotein endocytosis in liver cells in vitro. The model was tested for its ability to mimic known biochemical effects of familial hypercholesterolemia, statin therapy, and PCSK9 inhibitors. The model qualitatively reproduced the well-known biology of cholesterol regulation, which confirms its potential for minimizing cellular research in initial testing of new drugs for cardiology.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

A mathematical model of in vitro hepatocellular cholesterol and lipoprotein metabolism for hyperlipidemia therapy

et al. 2022

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“…The study marked a preliminary step for a complete development of perivascular system-on-chip [ 15 ]. OoAC platforms also provide the opportunity for personalized medicine as the human-induced pluripotent stem cells allow for the investigation of therapies that are tailored to specific patients or populations [ 16 , 17 ]. The global OoAC market has been steadily growing in recent years, primarily due to its drug discovery and testing applications, with an expected compound annual growth rate of 30% over the next five years [ 18 ].…”

Section: Introductionmentioning

confidence: 99%

Microfluidic Organ-on-A-chip: A Guide to Biomaterial Choice and Fabrication

Cao

Zhang

Chen

et al. 2023

IJMS

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Organ-on-a-chip (OoAC) devices are miniaturized, functional, in vitro constructs that aim to recapitulate the in vivo physiology of an organ using different cell types and extracellular matrix, while maintaining the chemical and mechanical properties of the surrounding microenvironments. From an end-point perspective, the success of a microfluidic OoAC relies mainly on the type of biomaterial and the fabrication strategy employed. Certain biomaterials, such as PDMS (polydimethylsiloxane), are preferred over others due to their ease of fabrication and proven success in modelling complex organ systems. However, the inherent nature of human microtissues to respond differently to surrounding stimulations has led to the combination of biomaterials ranging from simple PDMS chips to 3D-printed polymers coated with natural and synthetic materials, including hydrogels. In addition, recent advances in 3D printing and bioprinting techniques have led to the powerful combination of utilizing these materials to develop microfluidic OoAC devices. In this narrative review, we evaluate the different materials used to fabricate microfluidic OoAC devices while outlining their pros and cons in different organ systems. A note on combining the advances made in additive manufacturing (AM) techniques for the microfabrication of these complex systems is also discussed.

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“…Experiments conducted in vitro play an invaluable role in the research pipeline. In vitro models, including 3D organoids, have recently attracted attention as methods which might reduce and eventually replace the use of animals in research [ 1 ]. However, challenges in translating findings from in vitro research to the clinic may hinder efforts to replace animal research.…”

Section: Introductionmentioning

confidence: 99%

Screening for in vitro systematic reviews: a comparison of screening methods and training of a machine learning classifier

et al. 2023

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Objective: Existing strategies to identify relevant studies for systematic review may not perform equally well across research domains. We compare four approaches based on either human or automated screening of either title and abstract or full text; and report the training of a machine learning algorithm to identify in vitro studies from bibliographic records. Methods: We used a systematic review of oxygen-glucose deprivation (OGD) in PC-12 cells to compare approaches. For human screening, two reviewers independently screened studies based on title and abstract or full text, with disagreements reconciled by a third. For automated screening, we applied text mining to either title and abstract or full text. We trained a machine learning algorithm with decisions from 2,000 randomly selected PubMed Central records enriched with a dataset of known in vitro studies. Results: Full text approaches performed best, with human (sensitivity 0.990, specificity 1.000, precision 0.994) outperforming text mining (sensitivity 0.972, specificity 0.980, precision 0.764). For title and abstract, text mining (sensitivity 0.890, specificity 0.995, precision 0.922) outperformed human screening (sensitivity 0.862, specificity 0.998, precision 0.975). At our target sensitivity of 95% the algorithm performed with specificity of 0.850 and precision of 0.700. Conclusion: In this in vitro systematic review, human screening based on title and abstract erroneously excluded 14% of relevant studies, perhaps because title and abstract provide an incomplete description of methods used. Our algorithm might be used as a first selection phase in in vitro systematic reviews to limit the extent of full text screening required.

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Stem cells, organoids, and organ-on-a-chip models for personalized in vitro drug testing

Cited by 25 publications

References 46 publications

A mathematical model of in vitro hepatocellular cholesterol and lipoprotein metabolism for hyperlipidemia therapy

A mathematical model of in vitro hepatocellular cholesterol and lipoprotein metabolism for hyperlipidemia therapy

Microfluidic Organ-on-A-chip: A Guide to Biomaterial Choice and Fabrication

Screening for in vitro systematic reviews: a comparison of screening methods and training of a machine learning classifier

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