Organs-on-a-chip models for biological research

Vunjak‐Novakovic, Gordana; Ronaldson-Bouchard, Kacey; Radišić, Milica

doi:10.1016/j.cell.2021.08.005

Cited by 145 publications

(96 citation statements)

References 105 publications

(161 reference statements)

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“…Clinically, a major challenge to understanding the TME is the limited ability to capture sequential tissue samples from cancer patients. However, recent advances in three-dimensional (3D) platforms like organ on a chip and microfluidic devices, as well as the development of humanized mouse models or explant 3D cultures model (patient- or mouse-derived tumor spheroids) ( Sanmamed and Chen, 2014 ; Zitvogel et al, 2016 ; Jenkins et al, 2018 ; Vunjak-Novakovic et al, 2021 ), can provide an excellent opportunity to bridge this gap. Collectively, these tools have been developed with the view that a better understanding of the interplay of bi-directional communication between the tumor and TME, and CSCs will help identify improved cancer therapies.…”

Section: Promise Of Probing the Cellular Nichementioning

confidence: 99%

Uncovering Pharmacological Opportunities for Cancer Stem Cells—A Systems Biology View

Correia

Weiskittel

Ung

et al. 2022

Front. Cell Dev. Biol.

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Cancer stem cells (CSCs) represent a small fraction of the total cancer cell population, yet they are thought to drive disease propagation, therapy resistance and relapse. Like healthy stem cells, CSCs possess the ability to self-renew and differentiate. These stemness phenotypes of CSCs rely on multiple molecular cues, including signaling pathways (for example, WNT, Notch and Hedgehog), cell surface molecules that interact with cellular niche components, and microenvironmental interactions with immune cells. Despite the importance of understanding CSC biology, our knowledge of how neighboring immune and tumor cell populations collectively shape CSC stemness is incomplete. Here, we provide a systems biology perspective on the crucial roles of cellular population identification and dissection of cell regulatory states. By reviewing state-of-the-art single-cell technologies, we show how innovative systems-based analysis enables a deeper understanding of the stemness of the tumor niche and the influence of intratumoral cancer cell and immune cell compositions. We also summarize strategies for refining CSC systems biology, and the potential role of this approach in the development of improved anticancer treatments. Because CSCs are amenable to cellular transitions, we envision how systems pharmacology can become a major engine for discovery of novel targets and drug candidates that can modulate state transitions for tumor cell reprogramming. Our aim is to provide deeper insights into cancer stemness from a systems perspective. We believe this approach has great potential to guide the development of more effective personalized cancer therapies that can prevent CSC-mediated relapse.

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Section: Promise Of Probing the Cellular Nichementioning

confidence: 99%

Uncovering Pharmacological Opportunities for Cancer Stem Cells—A Systems Biology View

Correia

Weiskittel

Ung

et al. 2022

Front. Cell Dev. Biol.

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“…In comparison, smaller microfluidic devices often do not support an open‐well design with easy access to embedded tissue. Open‐well devices facile easy tissue and media retrieval, whereas sealed devices enable more complex flow patterns with higher fluidic and environmental control [23].…”

Section: Multiorgan Microphysiological Systemsmentioning

confidence: 99%

Multiorgan microphysiological systems as tools to interrogate interorgan crosstalk and complex diseases

Trapečar

2021

FEBS Letters

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Metabolic and inflammatory disorders such as autoimmune and neurodegenerative diseases are increasing at alarming rates. Many of these are not tissue‐specific occurrences but complex, systemic pathologies of unknown origin for which no cure exists. Such complexity obscures causal relationships among factors regulating disease progression. Emerging technologies mimicking human physiology, such as microphysiological systems (MPSs), offer new possibilities to provide clarity in systemic metabolic and inflammatory diseases. Controlled interaction of multiple MPSs and the scalability of biological complexity in MPSs, supported by continuous multiomic monitoring, might hold the key to identifying novel relationships between interorgan crosstalk, metabolism, and immunity. In this perspective, I aim to discuss the current state of modeling multiorgan physiology and evaluate current opportunities and challenges.

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“…Human advanced in vitro models are becoming widespread tools to study cellular interactions and function in many organ-specific contexts [15]. This is made possible through technological advances in bioengineered microphysiological systems (MPS) that support three-dimensional (3D) cellular self-organization [16], such as microfluidics or 3D patterning [17,18] in combination with biocompatible hydrogels [19,20]. While these individual technological advances have progressed incrementally over decades, their combination was only achieved recently.…”

Section: Introductionmentioning

confidence: 99%

“…While these individual technological advances have progressed incrementally over decades, their combination was only achieved recently. Resulting MPS now facilitate the formation, maturation and maintenance of complex organotypic structures in well-defined and customizable microenvironments [18,21,22]. Human-based MPS have already been developed for tissues such as lung, gut, brain and tumors, yet few integrative models exist for ocular tissues and iBRB modeling [23,24].…”

Section: Introductionmentioning

confidence: 99%

Microphysiological Neurovascular Barriers to Model the Inner Retinal Microvasculature

Maurissen

Pavlou

Bichsel

et al. 2022

JPM

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Blood-neural barriers regulate nutrient supply to neuronal tissues and prevent neurotoxicity. In particular, the inner blood-retinal barrier (iBRB) and blood–brain barrier (BBB) share common origins in development, and similar morphology and function in adult tissue, while barrier breakdown and leakage of neurotoxic molecules can be accompanied by neurodegeneration. Therefore, pre-clinical research requires human in vitro models that elucidate pathophysiological mechanisms and support drug discovery, to add to animal in vivo modeling that poorly predict patient responses. Advanced cellular models such as microphysiological systems (MPS) recapitulate tissue organization and function in many organ-specific contexts, providing physiological relevance, potential for customization to different population groups, and scalability for drug screening purposes. While human-based MPS have been developed for tissues such as lung, gut, brain and tumors, few comprehensive models exist for ocular tissues and iBRB modeling. Recent BBB in vitro models using human cells of the neurovascular unit (NVU) showed physiological morphology and permeability values, and reproduced brain neurological disorder phenotypes that could be applicable to modeling the iBRB. Here, we describe similarities between iBRB and BBB properties, compare existing neurovascular barrier models, propose leverage of MPS-based strategies to develop new iBRB models, and explore potentials to personalize cellular inputs and improve pre-clinical testing.

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Organs-on-a-chip models for biological research

Cited by 145 publications

References 105 publications

Uncovering Pharmacological Opportunities for Cancer Stem Cells—A Systems Biology View

Uncovering Pharmacological Opportunities for Cancer Stem Cells—A Systems Biology View

Multiorgan microphysiological systems as tools to interrogate interorgan crosstalk and complex diseases

Microphysiological Neurovascular Barriers to Model the Inner Retinal Microvasculature

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