Analysis of an Integrated Human Multiorgan Microphysiological System for Combined Tolcapone Metabolism and Brain Metabolomics

Wang, Xin; Cirit, Murat; Wishnok, John S.; Griffith, Linda G.; Tannenbaum, Steven R.

doi:10.1021/acs.analchem.9b02224

Cited by 35 publications

(31 citation statements)

References 48 publications

(83 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The platform was used to create an extensive metabolite profile and metabolomics of tolcapone, a drug used in Parkinson's disease management. The study identified 12 metabolites and reactions responsible for their generation 60 . This suggests that such multi‐organ platforms involving a liver component are suitable for comprehensive drug metabolism investigations and have the potential in the domain of analytical chemistry.…”

Section: Multi‐organ Platforms Integrating Locmentioning

confidence: 91%

“…Several studies demonstrate more complex MPSs integrating three, six or seven organs 56,60‐64 . Wang and colleagues employed a multi‐organ human‐on‐a‐chip integrating seven interacting MPSs: brain, pancreas, liver, lung, heart, gut, endometrium and a mixer chamber emulating systemic circulation (Figure 2B).…”

Section: Multi‐organ Platforms Integrating Locmentioning

confidence: 99%

“…59 Several studies demonstrate more complex MPSs integrating three, six or seven organs. 56,[60][61][62][63][64] Wang and colleagues employed a multi-organ human-on-a-chip integrating seven interacting MPSs: brain, pancreas, liver, lung, heart, gut, endometrium and a mixer chamber emulating systemic circulation (Figure 2B). The platform was used to create an extensive metabolite profile and metabolomics of tolcapone, a drug used in Parkinson's disease management.…”

Section: Ta B L E 2 (Continued)mentioning

confidence: 99%

See 2 more Smart Citations

Liver microphysiological platforms for drug metabolism applications

Kulsharova

Kurmangaliyeva

2021

Cell Proliferation

View full text Add to dashboard Cite

Drug development is a costly and lengthy process with low success rates. To improve the efficiency of drug development, there has been an increasing need in developing alternative methods able to eliminate toxic compounds early in the drug development pipeline. Drug metabolism plays a key role in determining the efficacy of a drug and its potential side effects. Since drug metabolism occurs mainly in the liver, liver cell‐based alternative engineering platforms have been growing in the last decade. Microphysiological liver cell‐based systems called liver‐on‐a‐chip platforms can better recapitulate the environment for human liver cells in laboratory settings and have the potential to reduce the number of animal models used in drug development by predicting the response of the liver to a drug in vitro. In this review, we discuss the liver microphysiological platforms from the perspective of drug metabolism studies. We highlight the stand‐alone liver‐on‐a‐chip platforms and multi‐organ systems integrating liver‐on‐a‐chip devices used for drug metabolism mimicry in vitro and review the state‐of‐the‐art platforms reported in the last few years. With the development of more robust and reproducible liver cell‐based microphysiological platforms, the drug development field has the potential of reducing the costs and lengths associated with currently existing drug testing methods.

show abstract

Section: Multi‐organ Platforms Integrating Locmentioning

confidence: 91%

Section: Multi‐organ Platforms Integrating Locmentioning

confidence: 99%

Section: Ta B L E 2 (Continued)mentioning

confidence: 99%

See 1 more Smart Citation

Liver microphysiological platforms for drug metabolism applications

Kulsharova

Kurmangaliyeva

2021

Cell Proliferation

View full text Add to dashboard Cite

show abstract

“…Such small molecule and multi-omic profiling can be accomplished using small sample volumes (<60 µL) [37,84,[89][90][91]. This allows for non-endpoint characterization of basal, diseased, drug-treated, or toxicant-challenged conditions over time as has been successfully conducted by multiple research groups using integrated multi-organ-on-a-chip models [83,92,93].…”

Section: Metabolic Functionality and Response Assessmentmentioning

confidence: 99%

Translational Roadmap for the Organs-on-a-Chip Industry toward Broad Adoption

et al. 2020

View full text Add to dashboard Cite

Organs-on-a-Chip (OOAC) is a disruptive technology with widely recognized potential to change the efficiency, effectiveness, and costs of the drug discovery process; to advance insights into human biology; to enable clinical research where human trials are not feasible. However, further development is needed for the successful adoption and acceptance of this technology. Areas for improvement include technological maturity, more robust validation of translational and predictive in vivo-like biology, and requirements of tighter quality standards for commercial viability. In this review, we reported on the consensus around existing challenges and necessary performance benchmarks that are required toward the broader adoption of OOACs in the next five years, and we defined a potential roadmap for future translational development of OOAC technology. We provided a clear snapshot of the current developmental stage of OOAC commercialization, including existing platforms, ancillary technologies, and tools required for the use of OOAC devices, and analyze their technology readiness levels. Using data gathered from OOAC developers and end-users, we identified prevalent challenges faced by the community, strategic trends and requirements driving OOAC technology development, and existing technological bottlenecks that could be outsourced or leveraged by active collaborations with academia.

show abstract

“…8,9 Electrical impedance spectroscopy (EIS) is a label-free characterization method that has been used for the investigation of different biological samples, ranging from single cells and 2D cell monolayers to multicellular constructs and organisms. [10][11][12][13][14] EIS can be used to measure the dielectric properties of a sample under investigation by applying an AC electric field at different frequencies across the sample through a set of electrodes. 15 Tissue apoptosis upon drug exposure, for example, could be detected by analyzing the variations in the impedance spectrum of a spheroid in a small microcavity featuring electrodes on the sidewalls.…”

mentioning

confidence: 99%

Parallelized Wireless Sensing System for Continuous Monitoring of Microtissue Spheroids

et al. 2020

View full text Add to dashboard Cite

Currently, the use of electrical readout methods for the investigation of microtissue spheroids in combination with lab automation tools is hindered by the cable connections that are required to interrogate the on-chip-integrated electrodes. To overcome this limitation, we developed a wireless sensor scheme, which can detect the size variation of microtissues during long-term culturing and drug exposure assays. The sensor system includes an interrogation board, which is composed by an inductor-capacitor (LC) readout circuit, and the tissue culture platform with integrated split-ring sensors. The magnetic coupling between the LC circuit and the sensors enables the interrogation of the on-chip sensors without any wire connection to the culture platform. By optimizing the sensor dimensions and the LC resonance frequencies, we were able to avoid cross talk between neighboring sensors. We integrated 12 tissue compartments on a standard microscopy slide with a sensor-to-sensor pitch of 9 mm, which is in accordance with standard 96 well-plate dimensions. As proof-of-concept experiment for the developed system, we monitored continuously and during more than four days the growth inhibition of colon-cancer microtissue spheroids that had been exposed to different concentration of doxorubicin, a chemotherapeutic compound. The stability of the measurements during long-term culturing and the compatibility of the sensor scheme with standard lab equipment offers great potential for automated electrical microtissue spheroid characterization.

show abstract

Analysis of an Integrated Human Multiorgan Microphysiological System for Combined Tolcapone Metabolism and Brain Metabolomics

Cited by 35 publications

References 48 publications

Liver microphysiological platforms for drug metabolism applications

Liver microphysiological platforms for drug metabolism applications

Translational Roadmap for the Organs-on-a-Chip Industry toward Broad Adoption

Parallelized Wireless Sensing System for Continuous Monitoring of Microtissue Spheroids

Contact Info

Product

Resources

About