Liver-on-a-chip platform to study anticancer effect of statin and its metabolites

Chen, Pin-Yao; Hsieh, Meng-Ju; Liao, Ying-Hsiu; Lin, Yu-Che; Hou, Yung-Te

doi:10.1016/j.bej.2020.107831

Cited by 23 publications

(11 citation statements)

References 43 publications

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“…The liver is greatly affected by treatments since it is involved in drug metabolism. Some drugs are activated after the biotransformation in the liver [ 54 ]. Liang et al [ 48 ] designed a microfluidic device ( Figure 6 c) with an integrated light addressable potentiometric sensor to monitor the pH and, consequently, the metabolism of the cell culture.…”

Section: Resultsmentioning

confidence: 99%

“…On the other hand, no effects were reported on the gastric cells. Chen et al [ 54 ] presented a microfluidic system that incorporated a liver-on-a-chip (LOC) connected to a tumor-on-chip to evaluate the effects of statin and its respective metabolites on healthy and tumor cell lines. The expression of metabolic markers on the LOC increased when connected to the cancer culture.…”

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

Organ-on-a-Chip Platforms for Drug Screening and Delivery in Tumor Cells: A Systematic Review

Gonçalves

Carvalho

Rodrigues

et al. 2022

Cancers

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The development of cancer models that rectify the simplicity of monolayer or static cell cultures physiologic microenvironment and, at the same time, replicate the human system more accurately than animal models has been a challenge in biomedical research. Organ-on-a-chip (OoC) devices are a solution that has been explored over the last decade. The combination of microfluidics and cell culture allows the design of a dynamic microenvironment suitable for the evaluation of treatments’ efficacy and effects, closer to the response observed in patients. This systematic review sums the studies from the last decade, where OoC with cancer cell cultures were used for drug screening assays. The studies were selected from three databases and analyzed following the research guidelines for systematic reviews proposed by PRISMA. In the selected studies, several types of cancer cells were evaluated, and the majority of treatments tested were standard chemotherapeutic drugs. Some studies reported higher drug resistance of the cultures on the OoC devices than on 2D cultures, which indicates the better resemblance to in vivo conditions of the former. Several studies also included the replication of the microvasculature or the combination of different cell cultures. The presence of vasculature can influence positively or negatively the drug efficacy since it contributes to a greater diffusion of the drug and also oxygen and nutrients. Co-cultures with liver cells contributed to the evaluation of the systemic toxicity of some drugs metabolites. Nevertheless, few studies used patient cells for the drug screening assays.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Organ-on-a-Chip Platforms for Drug Screening and Delivery in Tumor Cells: A Systematic Review

Gonçalves

Carvalho

Rodrigues

et al. 2022

Cancers

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show abstract

“…Similarly, Benam et al developed smoking human small airway lung-OOC to realize the analysis of the effects of whole smoke, as presented in Fig. 9(b) [121]. The engineered chip possessed traditional upper-lower microchannels separated with a thin porous membrane which was cultured with living human bronchiolar epithelium cells from individuals with or without smoke exposure.…”

Section: Lung-on-a-chipmentioning

confidence: 99%

Sensors-integrated organ-on-a-chip for biomedical applications

et al. 2023

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As a promising new micro-physiological system, organ-on-a-chip has been widely utilized for in vitro pharmaceutical study and tissues engineering based on the three-dimensional constructions of tissues/organs and delicate replication of in vivo -like microenvironment. To better observe the biological processes, a variety of sensors have been integrated to realize in-situ , real-time, and sensitive monitoring of critical signals for organs development and disease modeling. Herein, we discuss the recent research advances made with respect to sensors-integrated organ-on-a-chip in this overall review. Firstly, we briefly explore the underlying fabrication procedures of sensors within microfluidic platforms and several classifications of sensory principles. Then, emphasis is put on the highlighted applications of different types of organ-on-a-chip incorporated with various sensors. Last but not least, perspective on the remaining challenges and future development of sensors-integrated organ-on-a-chip are presented.

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“…MPSs of nearly every major human organ including hosting liver (Asif et al, 2021, Chen et al, 2021, Ewart et al, 2022, Görgens et al, 2021, Takebe et al, 2013), lung (Sachs et al, 2019, Ainslie et al, 2019), intestine (Sato et al, 2009, Peters et al, 2020, Jalili-Firoozinezhad et al, 2019), neural (Lancaster et al, 2013, Liu et al, 2019, Pamies et al, 2017) and cardiac tissue (Rogozhnikov et al, 2016, Conant et al, 2017, Lind et al, 2017) (amongst many others) have been developed using cells from a variety of sources including cell lines, primary cells and stem cells and have been grown using single or multiple cell types. The complexity that brings power and versatility of these systems comes with the challenge of having to define, mature and measure outcomes in a meaningful and well controlled manner.…”

Section: Introductionmentioning

confidence: 99%

Mera: A scalable high throughput automated micro-physiological system

Cliffe¹,

Costello²,

Madden³

et al. 2022

Preprint

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There is an urgent need for scalable Microphysiological Systems (MPSs) that can better predict drug efficacy and toxicity at the preclinical screening stage. Here we present Mera, an automated, modular and scalable system for culturing and assaying microtissues with inbuilt environment control and automated image capture. The paradigm presented involves culturing and maturing common microtissue types in rows (rows of e.g., liver, heart, gastro-intestinal or kidney microtissues) and then reorienting fluid flow to create a recirculating circuit composed of inter-connected columns containing distinct microtissues (e.g. individual fluidic circuits with liver, heart, gastrointestinal and kidney micro-tissues inter-connected) to allow drugging or staining. We present data demonstrating the prototype system using an Acetaminophen/HepG2 liver microtissue toxicity assay with Calcein AM and Ethidium Homodimer viability assays. We demonstrate the functionality of the automated image capture system. The prototype microtissue culture plate wells are laid out in a 3x3 or 4x10 grid with viability and toxicity assays demonstrated in both formats. In this paper we set the groundwork for the Mera system as a viable option for scalable microtissue culture and assay development.

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Liver-on-a-chip platform to study anticancer effect of statin and its metabolites

Cited by 23 publications

References 43 publications

Organ-on-a-Chip Platforms for Drug Screening and Delivery in Tumor Cells: A Systematic Review

Organ-on-a-Chip Platforms for Drug Screening and Delivery in Tumor Cells: A Systematic Review

Sensors-integrated organ-on-a-chip for biomedical applications

Mera: A scalable high throughput automated micro-physiological system

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