Efficient Drug Screening and Nephrotoxicity Assessment on Co-culture Microfluidic Kidney Chip

Abstract

The function and susceptibility of various drugs are tested with renal proximal tubular epithelial cells; yet, replicating the morphology and kidneys function using the currently available in vitro models remains difficult. To overcome this difficulty, in the study presented in this paper, a device and a threelayer microfluidic chip were developed, which provides a simulated environment for kidney organs. This device includes two parts: (1) microfluidic drug concentration gradient generator and (2) a flowtemperature controlled platform for culturing of kidney cells. In chip study, renal proximal tubular epithelial cells (RPTECs) and peritubular capillary endothelial cells (PCECs) were screened with the drugs to assess the drug-induced nephrotoxicity. Unlike cells cultured in petri dishes, cells cultured in the microfluidic device exhibited higher performance in terms of both cell growth and drug nephrotoxicity evaluation. It is worth mentioning that a significant decrease in cisplatin-induced nephrotoxicity was found because of the intervention of cimetidine in the microfluidic device. In conclusion, the different in the cell performance between the microfluidic device and the petri dishes demonstrates the physiological relevance of the nephrotoxicity screening technology along with the microfluidic device developed in this study. Furthermore, this technology can also facilitate the development of reliable kidney drugs and serve as a useful and efficient test-bed for further investigation of the drug nephrotoxicity evaluation.

Fabrication and Applications of Microfluidic Devices: A Review

“…Kidney-on-a-chip platforms have also attracted significant attention in the field of microfluidics, imitating the real renal tubular cell environment [ 102 ]. Yin et al [ 103 ] built a three-layer microfluidic kidney chip that integrated PDMS microchannels and porous membranes, also developing a supporting microfluidic culture platform that enabled the long-term culture of renal cells ( Figure 5 ).…”

Advances in Engineering Human Tissue Models

“…Even though most of the attention OOCs have gained is focused on pharmacology and pre-clinical drug screening applications, as low-cost and animal-free alternative tool (Ramadan and Zourob, 2020 ), it is clear that the principle behind this technology lines perfectly with the TE paradigm and scope: convergence of cells with the advanced chip technology-biomaterials and delivery of physiologically relevant cues toward more robust tissue equivalents. As a result, various research groups around the world, both in the academic and industrial sectors, have developed a broad range of OOCs, mimicking the human gut (Ramadan and Jing, 2016 ; Kasendra et al, 2018 ; Shin et al, 2019 ), liver (Delalat et al, 2018 ; Jang et al, 2019 ), kidney (Jang et al, 2013 ; Chang et al, 2017 ; Yin et al, 2020 ), lung (Huh et al, 2012 ; Stucki et al, 2018 ; Felder et al, 2019 ), blood-brain barrier (Kilic et al, 2016 ; Wevers et al, 2018 ), bone (Marturano-Kruik et al, 2018 ), and vasculature (Schimek et al, 2013 ; Jeon et al, 2015 ) in both healthy and pathophysiological conditions, such as infection (Villenave et al, 2017 ; Ortega-Prieto et al, 2018 ) and cancer (Ayuso et al, 2016 ; Hassell et al, 2017 ; Hao et al, 2018 ; Carvalho et al, 2019 ), as well as for the interaction of multiple organs, as first showcased by Shuler et al and more recently by others, toward multi-organ and whole-body microsystems (Miller and Shuler, 2016 ; Vernetti et al, 2017 ; Edington et al, 2018 ; Herland et al, 2020 ), to study collective responses to drugs or disease inducing agents and inter-organ communication.…”

Organ-on-a-Chip systems for new drugs development

“…Some examples of this technology can be found in the work of Yin et al, who developed a kidney-on-achip device for drug screening and nephrotoxicity assessment (figure 5). They achieved tissue differentiation and functionality by growing the two cell cultures on opposite membranes, and evaluated the cell growth and viability using fluorescent markers [97]. On the other hand, Jang et al built a system for drug transport and nephrotoxicity assessment in preclinical phases that mimicked key functions of the human kidney proximal tubule.…”