In vitro metabolic activation of vitamin D3 by using a multi-compartment microfluidic liver-kidney organ on chip platform

Theobald, Jannick; Maaty, Mohamed A. Abu el; Kusterer, Nico; Wetterauer, Bernhard; Cheng, Xinlai; Wölfl, Stefan

doi:10.1038/s41598-019-40851-9

Cited by 42 publications

(34 citation statements)

References 34 publications

(39 reference statements)

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“…The results show that in this model, the toxicity and metabolic response of drugs can be evaluated in a flow-controlled manner. Later, the team set up a multi-chamber liver-kidney chip to study drug metabolism in vitro [141]. The pump-driven vitamin D3-containing culture medium produced an eluate containing vitamin D3 metabolites through a microfluidic chip, where LC-MS/MS showed strong 25-hydroxyvitamin D accumulation.…”

Section: Liver-kidney-on-chipmentioning

confidence: 99%

Drug Toxicity Evaluation Based on Organ-on-a-chip Technology: A Review

Han

Wang

et al. 2020

Micromachines

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Organ-on-a-chip academic research is in its blossom. Drug toxicity evaluation is a promising area in which organ-on-a-chip technology can apply. A unique advantage of organ-on-a-chip is the ability to integrate drug metabolism and drug toxic processes in a single device, which facilitates evaluation of toxicity of drug metabolites. Human organ-on-a-chip has been fabricated and used to assess drug toxicity with data correlation with the clinical trial. In this review, we introduced the microfluidic chip models of liver, kidney, heart, nerve, and other organs and multiple organs, highlighting the application of these models in drug toxicity detection. Some biomarkers of toxic injury that have been used in organ chip platforms or have potential for use on organ chip platforms are summarized. Finally, we discussed the goals and future directions for drug toxicity evaluation based on organ-on-a-chip technology.

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Section: Liver-kidney-on-chipmentioning

confidence: 99%

Drug Toxicity Evaluation Based on Organ-on-a-chip Technology: A Review

Han

Wang

et al. 2020

Micromachines

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“…Moreover, complex metabolic interactions were reconstructed by using dedicated organ-on-a-chip platforms. A recent example is the use of a multi-compartment microfluidic chip to recapitulate hepatic vitamin D metabolism and renal bio-activation [131]. However, many challenges have to be overcome because the structural and functional complexity of kidney make the development of a true kidney-on-a-chip more than just a sum of individual nephron components.…”

Section: Tubule-on-a-chipmentioning

confidence: 99%

Bioengineering strategies for nephrologists: kidney was not built in a day

Peired

Mazzinghi

Chiara

et al. 2020

Expert Opinion on Biological Therapy

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Introduction: The number of patients with end-stage kidney disease is increasing worldwide, creating an unprecedented organ shortage. The kidney is a highly complex structure performing many crucial functions. Dialysis replaces filtration but not all other kidney functions and transplant is limited by kidney availability. Numerous innovative ways are being explored to obtain new kidneys for disease modeling and potentially replace lost kidney functions. Areas covered: In this review, we will go through the different approaches that have been developed over the years to build kidneys. We will first present the current advances in xenotransplantation and generation of interspecies chimeras. Next, we will examine the attempts to create bioengineered kidneys with hemodialysis-derived implantable devices and decellularized organs. Finally, we will examine how organoids and microfluidic devices could answer important pathophysiological questions and model the path toward creating in vitro functional organs, for example through 3D bioprinting. Expert opinion: While all the aforementioned approaches to create new kidneys are promising, their translation into clinical practice seems a long way off, except xenotransplantation. Nonetheless, these novel technologies already consent disease modeling and drug testing at 3D level. We will review the stages of progress toward patient therapy and advantages/drawbacks of the various strategies.

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“…Table 1. Advanced liver-on-a-chip devices to study hepatic functions and liver-based multi-organ communication [53][54][55][56][57][58][59][60][61][62][63][64][65][66][67][68][69].…”

Section: Devices To Model the Liver: Features And Cell Componentsmentioning

confidence: 99%

“…HepaRG cell line + primary normal human bronchial epithelial (NHBE) cells [68] Multi organ-on-a-chip mimicking the interaction between lung and kidney HepG2 cell line + primary renal proximal tubule epithelial (RPTEC) cells [69] In the last few years, these miniaturized technologies have overcome the limitations of 2D in vitro cultures. In fact, the 2D hepatocyte monolayers generally used to reproduce hepatic functions are not exposed to the complex extracellular matrix and intercellular interactions of their native in vivo microenvironment.…”

Section: Primary Human Hepatocytes Both Monocultured and Cocultured Withmentioning

confidence: 99%

“…Initially, it was assimilated by the liver cells, then transported to the kidney chamber, where it was metabolized to 1,25(OH)2D3. After treatment with the eluted 1,25(OH)2D3, HL-60 human leukemia cells showed a pro-differentiation effect confirmed by the expression of differentiation markers [69]. Theobald and colleagues proposed an optically accessible device and subjected the cells to a continuous flow of fresh medium.…”

Section: Liver-based Multi-organ-on-a-chip Platformsmentioning

confidence: 99%

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Advanced Organ-on-a-Chip Devices to Investigate Liver Multi-Organ Communication: Focus on Gut, Microbiota and Brain

et al. 2019

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The liver is a key organ that can communicate with many other districts of the human body. In the last few decades, much interest has focused on the interaction between the liver and the gut microbiota, with their reciprocal influence on biosynthesis pathways and the integrity the intestinal epithelial barrier. Dysbiosis or liver disorders lead to0 epithelial barrier dysfunction, altering membrane permeability to toxins. Clinical and experimental evidence shows that the permeability hence the delivery of neurotoxins such as LPS, ammonia and salsolinol contribute to neurological disorders. These findings suggested multi-organ communication between the gut microbiota, the liver and the brain. With a view to in vitro modeling this liver-based multi-organ communication, we describe the latest advanced liver-on-a-chip devices and discuss the need for new organ-on-a-chip platforms for in vitro modeling the in vivo multi-organ connection pathways in physiological and pathological situations.

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In vitro metabolic activation of vitamin D3 by using a multi-compartment microfluidic liver-kidney organ on chip platform

Cited by 42 publications

References 34 publications

Drug Toxicity Evaluation Based on Organ-on-a-chip Technology: A Review

Drug Toxicity Evaluation Based on Organ-on-a-chip Technology: A Review

Bioengineering strategies for nephrologists: kidney was not built in a day

Advanced Organ-on-a-Chip Devices to Investigate Liver Multi-Organ Communication: Focus on Gut, Microbiota and Brain

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