Rhythm on a chip: circadian entrainment in vitro is the next frontier in body-on-a chip technology

Fustin, Jean‐Michel; Li, Meina; Gao, Xumei; Chen, Qianyu; Cheng, Tianhong; Stewart, Alastair G.

doi:10.1016/j.coph.2019.09.005

Cited by 11 publications

(10 citation statements)

References 71 publications

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“…[63] Applied to cancer cell research, circadian rhythm stimulation may be an essential step for improving on-chip models to predict responses from cancer growth to the susceptibility to anti-cancer drugs since circadian rhythms impact those responses and have been typically overlooked in in vitro models. [64,65] Beyond cells alone, intratumoral interactions between cancer cells and noncellular components of TME significantly mediate cancer aggressiveness. Specifically, the establishment of solid stress induces a hyper-response from stroma, resulting in an alteration of ECM stiffness.…”

Section: Light-driven Recreation Of Cancer-like Microenvironments: Fr...mentioning

confidence: 99%

“…[ 63 ] Applied to cancer cell research, circadian rhythm stimulation may be an essential step for improving on‐chip models to predict responses from cancer growth to the susceptibility to anti‐cancer drugs since circadian rhythms impact those responses and have been typically overlooked in in vitro models. [ 64,65 ]…”

Section: Light‐driven Recreation Of Cancer‐like Microenvironments: Fr...mentioning

confidence: 99%

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Shining a Light on Cancer—Photonics in Microfluidic Tumor Modeling and Biosensing

Guimarães

Cruz‐Moreira

Caballero

et al. 2022

Adv Healthcare Materials

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Microfluidic platforms represent a powerful approach to miniaturizing important characteristics of cancers, improving in vitro testing by increasing physiological relevance. Different tools can manipulate cells and materials at the microscale, but few offer the efficiency and versatility of light and optical technologies. Moreover, light‐driven technologies englobe a broad toolbox for quantifying critical biological phenomena. Herein, the role of photonics in microfluidic 3D cancer modeling and biosensing from three major perspectives is reviewed. First, optical‐driven technologies are looked upon, as these allow biomaterials and living cells to be manipulated with microsized precision and present opportunities to advance 3D microfluidic models by engineering cancer microenvironments' hallmarks, such as their architecture, cellular complexity, and vascularization. Second, the growing field of optofluidics is discussed, exploring how optical tools can directly interface microfluidic chips, enabling the extraction of relevant biological data, from single fluorescent signals to the complete 3D imaging of diseased cells within microchannels. Third, advances in optical cancer biosensing are reviewed, focusing on how light–matter interactions can detect biomarkers, rare circulating tumor cells, and cell‐derived structures such as exosomes. Photonic technologies' current challenges and caveats in microfluidic 3D cancer models are overviewed, outlining future research avenues that may catapult the field.

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Section: Light-driven Recreation Of Cancer-like Microenvironments: Fr...mentioning

confidence: 99%

Section: Light‐driven Recreation Of Cancer‐like Microenvironments: Fr...mentioning

confidence: 99%

Shining a Light on Cancer—Photonics in Microfluidic Tumor Modeling and Biosensing

Guimarães

Cruz‐Moreira

Caballero

et al. 2022

Adv Healthcare Materials

View full text Add to dashboard Cite

show abstract

“…However, current technologies do not replicate circadian rhythmicity and this limits their predictive value in situations where the target physiology has a circadian component. The incorporation of relevant timing cues into predictive in vitro model systems is a concept that has received limited attention to date, in part due to the technical challenges of recapitulating the circadian profile of synchronising endocrine signals such as cortisol within these systems [ 18 , 19 ]. However, the application of appropriate timing cues represents an important area of development to introduce a key component of in vivo physiology into OOAC technology and other predictive in vitro systems (Fig.…”

Section: Introductionmentioning

confidence: 99%

Oscillations of the circadian clock protein, BMAL-1, align to daily cycles of mechanical stimuli: a novel means to integrate biological time within predictive in vitro model systems

et al. 2022

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Purpose In vivo, the circadian clock drives 24-h rhythms in human physiology. Isolated cells in vitro retain a functional clockwork but lack necessary timing cues resulting in the rapid loss of tissue-level circadian rhythms. This study tests the hypothesis that repeated daily mechanical stimulation acts as a timing cue for the circadian clockwork. The delineation and integration of circadian timing cues into predictive in vitro model systems, including organ-on-a-chip (OOAC) devices, represent a novel concept that introduces a key component of in vivo physiology into predictive in vitro model systems. Methods Quiescent bovine chondrocytes were entrained for 3 days by daily 12-h bouts of cyclic biaxial tensile strain (10%, 0.33 Hz, Flexcell) before sampling during free-running conditions. The core clock protein, BMAL-1, was quantified from normalised Western Blot signal intensity and the temporal oscillations characterised by Cosinor linear fit with 24-h period. Results Following entrainment, the cell-autonomous oscillations of the molecular clock protein, BMAL-1, exhibited circadian (24 h) periodicity (p < 0.001) which aligned to the diurnal mechanical stimuli. A 6-h phase shift in the mechanical entrainment protocol resulted in an equivalent shift of the circadian clockwork. Thus, repeated daily mechanical stimuli synchronised circadian rhythmicity of chondrocytes in vitro. Conclusion This work demonstrates that daily mechanical stimulation can act as a timing cue that is sufficient to entrain the peripheral circadian clock in vitro. This discovery may be exploited to induce and sustain circadian physiology within into predictive in vitro model systems, including OOAC systems. Integration of the circadian clock within these systems will enhance their potential to accurately recapitulate human diurnal physiology and hence augment their predictive value as drug testing platforms and as realistic models of human (patho)physiology.

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“…However, due to cost, practicality and the apparent efficiency of highly parallel technologies in current biomedical and clinical research, almost all in vitro cell culture work is carried out in an unphysiological and static environment, as differentiated from the characteristic dynamic in vivo condition. 6–8 There is also a general neglect in controlling and monitoring cell culture environmental variables in biomedical research, evoking reproducibility concerns. 9 The collective artificiality inevitably compromises the predictive value of the data derived, thereby placing a low ceiling on the utility of in vitro culture, especially in mid- to long-term experimentation.…”

Section: Introductionmentioning

confidence: 99%

Comprehensive multiplexed superfusion system enables physiological emulation in cell culture: exemplification by persistent circadian entrainment

Gao

Cheng

et al. 2022

Lab Chip

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Rhythm on a chip: circadian entrainment in vitro is the next frontier in body-on-a chip technology

Cited by 11 publications

References 71 publications

Shining a Light on Cancer—Photonics in Microfluidic Tumor Modeling and Biosensing

Shining a Light on Cancer—Photonics in Microfluidic Tumor Modeling and Biosensing

Oscillations of the circadian clock protein, BMAL-1, align to daily cycles of mechanical stimuli: a novel means to integrate biological time within predictive in vitro model systems

Comprehensive multiplexed superfusion system enables physiological emulation in cell culture: exemplification by persistent circadian entrainment

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