Membrane-free culture and real-time barrier integrity assessment of perfused intestinal epithelium tubes

Trietsch, Bas; Naumovska, Elena; Kurek, Dorota; Saleh, Anthony; Lanz, Henriëtte L.; Joore, Jos; Kustermann, Stefan; Roth, Adrian; Moisan, Annie; Vulto, Paul

doi:10.1016/j.dmpk.2017.11.160

Cited by 2 publications

(2 citation statements)

References 17 publications

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“…Both these systems are compatible with medium-to high-throughput screening and image analysis and could be promptly implemented in the drug screening process. Cell culture in the OrganoPlate offers the additional advantages of allowing culture under more physiological flow conditions and the parallel assessment of functional aspects such as epithelial barrier function (45). miRNAs are attractive biomarkers since they can be measured without interrupting the exposure and are relatively easy to quantify using accessible molecular biology methods such as qPCR and NexGen sequencing.…”

Section: Discussionmentioning

confidence: 99%

Combining Extracellular miRNA Determination with Microfluidic 3D Cell Cultures for the Assessment of Nephrotoxicity: a Proof of Concept Study

Suter‐Dick

Mauch

Ramp

et al. 2018

AAPS J

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Abstract.Drug-induced kidney injury is often observed in the clinics and can lead to longterm organ failure. In this work, we evaluated a novel in vitro system that aims at detecting whether compounds can cause renal proximal tubule damage in man. For this, we implemented organotypic cultures of human conditionally immortalized proximal tubule epithelial cells overexpressing the organic anion transporter 1 (ciPTEC-OAT1) in a threechannel OrganoPlate under microfluidic conditions. Cells were exposed to four known nephrotoxicants (cisplatin, tenofovir, cyclosporine A, and tobramycin). The effect on cell viability and NAG release into the medium was determined. A novel panel of four miRNAs (mir-21, mir-29a, mir-34a, and mir-192) was selected as potential biomarkers of proximal tubule damage. After nephrotoxicant treatment, miRNA levels in culture medium were earlier indicators than cell viability (WST-8 assay) and outperformed NAG for proximal tubule damage. In particular, mir-29a, mir-34a, and mir-192 were highly reproducible between experiments and across compounds, whereas mir-21 showed more variability. Moreover, similar data were obtained in two different laboratories, underlining the reproducibility and technical transferability of the results, a key requirement for the implementation of novel biomarkers. In conclusion, the selected miRNAs behaved like sensitive biomarkers of damage to tubular epithelial cells caused by several nephrotoxicity mechanisms. This biomarker panel, in combination with the 3D cultures of ciPTEC-OAT1 in the OrganoPlate, represents a novel tool for in vitro nephrotoxicity detection. These results pave the way for the application of miRNAs in longitudinal, time-course in vitro toxicity studies.

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Section: Discussionmentioning

confidence: 99%

Combining Extracellular miRNA Determination with Microfluidic 3D Cell Cultures for the Assessment of Nephrotoxicity: a Proof of Concept Study

Suter‐Dick

Mauch

Ramp

et al. 2018

AAPS J

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“…Recently commercialized 3D cell culture platform, “Organoplate”, is capable of constructing 3D hydrogel structure without pillar structure. However, it still uses the structural strategy that consists of stripe protrusions on the bottom, which blocks more than 25% of the channel height 31–33 . Thus, there is a great need for new design strategies that enable uniform contact with and diffusion between cells and the ECM to better recapitulate in vivo conditions.…”

Section: Introductionmentioning

confidence: 99%

Hydrophobic Patterning‐Based 3D Microfluidic Cell Culture Assay

Han

Kim

et al. 2018

Adv Healthcare Materials

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Engineering physiologically relevant in vitro models of human organs remains a fundamental challenge. Despite significant strides made within the field, many promising organ-on-a-chip models fall short in recapitulating cellular interactions with neighboring cell types, surrounding extracellular matrix (ECM), and exposure to soluble cues due, in part, to the formation of artificial structures that obstruct >50% of the surface area of the ECM. Here, a 3D cell culture platform based upon hydrophobic patterning of hydrogels that is capable of precisely generating a 3D ECM within a microfluidic channel with an interaction area >95% is reported. In this study, for demonstrative purposes, type I collagen (COL1), Matrigel (MAT), COL1/MAT mixture, hyaluronic acid, and cell-laden MAT are formed in the device. Three potential applications are demonstrated, including creating a 3D endothelium model, studying the interstitial migration of cancer cells, and analyzing stem cell differentiation in a 3D environment. The hydrophobic patterned-based 3D cell culture device provides the ease-of-fabrication and flexibility necessary for broad potential applications in organ-on-a-chip platforms.

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Membrane-free culture and real-time barrier integrity assessment of perfused intestinal epithelium tubes

Cited by 2 publications

References 17 publications

Combining Extracellular miRNA Determination with Microfluidic 3D Cell Cultures for the Assessment of Nephrotoxicity: a Proof of Concept Study

Combining Extracellular miRNA Determination with Microfluidic 3D Cell Cultures for the Assessment of Nephrotoxicity: a Proof of Concept Study

Hydrophobic Patterning‐Based 3D Microfluidic Cell Culture Assay

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