Analysis of reproducibility and robustness of a human microfluidic four-cell liver acinus microphysiology system (LAMPS)

Sakolish, Courtney; Reese, Celeste E.; Luo, Yu‐Syuan; Valdiviezo, Alan; Schurdak, Mark E.; Gough, Albert; Taylor, D. Lansing; Chiu, Weihsueh A.; Vernetti, Lawrence A.; Rusyn, Ivan

doi:10.1016/j.tox.2020.152651

Cited by 27 publications

(29 citation statements)

References 49 publications

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“…The LAMPS has been tested and reproduced by the Texas A&M Tissue Chip Validation Center (Tex-Val) one of the National Center for Advancing Translational Sciences (NCATS) funded Tissue Chip Testing Centers (TCTC). 57 Results of that testing can also be found in the MPS-Database. 6,7,58 The vLAMPS (Figure 2(a)) uses a two channel glass device to create an upper hepatic channel and a lower vascular channel, separated by a 3-µm pore size PET membrane (shown as a red dotted line).…”

Section: Human Mps To Investigate Metabolic Syndromementioning

confidence: 99%

“…57 Results of that testing can also be found in the MPS-Database. 6,7,58 The vLAMPS (Figure 2(a)) uses a two channel glass device to create an upper hepatic channel and a lower vascular channel, separated by a 3-µm pore size PET membrane (shown as a red dotted line). The vLAMPS generates an oxygen gradient through the consumption of oxygen by the hepatocytes, recapitulating physiological zonation in the liver.…”

Section: Human Mps To Investigate Metabolic Syndromementioning

confidence: 99%

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Quantifying the progression of non-alcoholic fatty liver disease in human biomimetic liver microphysiology systems with fluorescent protein biosensors

Saydmohammed

Jha

Mahajan

et al. 2021

Exp Biol Med (Maywood)

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Metabolic syndrome is a complex disease that involves multiple organ systems including a critical role for the liver. Non-alcoholic fatty liver disease (NAFLD) is a key component of the metabolic syndrome and fatty liver is linked to a range of metabolic dysfunctions that occur in approximately 25% of the population. A panel of experts recently agreed that the acronym, NAFLD, did not properly characterize this heterogeneous disease given the associated metabolic abnormalities such as type 2 diabetes mellitus (T2D), obesity, and hypertension. Therefore, metabolic dysfunction-associated fatty liver disease (MAFLD) has been proposed as the new term to cover the heterogeneity identified in the NAFLD patient population. Although many rodent models of NAFLD/NASH have been developed, they do not recapitulate the full disease spectrum in patients. Therefore, a platform has evolved initially focused on human biomimetic liver microphysiology systems that integrates fluorescent protein biosensors along with other key metrics, the microphysiology systems database, and quantitative systems pharmacology. Quantitative systems pharmacology is being applied to investigate the mechanisms of NAFLD/MAFLD progression to select molecular targets for fluorescent protein biosensors, to integrate computational and experimental methods to predict drugs for repurposing, and to facilitate novel drug development. Fluorescent protein biosensors are critical components of the platform since they enable monitoring of the pathophysiology of disease progression by defining and quantifying the temporal and spatial dynamics of protein functions in the biosensor cells, and serve as minimally invasive biomarkers of the physiological state of the microphysiology system experimental disease models. Here, we summarize the progress in developing human microphysiology system disease models of NAFLD/MAFLD from several laboratories, developing fluorescent protein biosensors to monitor and to measure NAFLD/MAFLD disease progression and implementation of quantitative systems pharmacology with the goal of repurposing drugs and guiding the creation of novel therapeutics.

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Section: Human Mps To Investigate Metabolic Syndromementioning

confidence: 99%

Section: Human Mps To Investigate Metabolic Syndromementioning

confidence: 99%

Quantifying the progression of non-alcoholic fatty liver disease in human biomimetic liver microphysiology systems with fluorescent protein biosensors

Saydmohammed

Jha

Mahajan

et al. 2021

Exp Biol Med (Maywood)

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“…MPS is known to influence the yield of albumin by HepG2 cells greatly. Comparing the conventional cell culture model (96-well cell culture plate), liver tumor MPS showed a considerable difference in albumin release between the two cell culture models [10,31]. The albumin production by liver tumor MPS was onefold increased compared to the conventional cell culture model (Figure 2a,b).…”

Section: Effect Of a Cappadocicum On Liver Function Testsmentioning

confidence: 95%

Study of the Anticancer Potential of Plant Extracts Using Liver Tumor Microphysiological System

Farooqi

Sammantasinghar

Kausar

et al. 2022

Life

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Background: Plants have been considered a vital source of modern pharmaceutics since the paleolithic age. Contemporary chemotherapeutic drugs for cancer therapy are chemical entities sourced from plants. However, synthetic drugs or their derivatives come with severe to moderate side effects for human health. Hence, the quest to explore and discover plant-based novel anticancer drugs is ongoing. Anticancer activities are the primary method to estimate the potential and efficacy of an extract or compound for drug discovery. However, traditional in vitro anticancer activity assays often show poor efficacy due to the lack of in-vivo-like cellular environment. In comparison, the animal-based in vivo assays lack human genetic makeup and have ethical concerns. Aim: This study aimed to overcome the limitations of traditional cell-culture-based anticancer assays and find the most suitable assay for anticancer activity of plant extracts. We first reported utilizing a liver tumor microphysiological system in the anticancer effect assessment of plant extracts. Methodology: Methanolic extracts of Acer cappadocicum Gled were used to assess anticancer activity against liver tumor microphysiological system (MPS), and cell viability, liver function tests, and antioxidant enzyme activities were performed. Additionally, an embedded transepithelial electrical resistance sensor was utilized for the real-time monitoring of the liver tumor MPS. The results were also compared with the traditional cell culture model. Results: The study demonstrated the superiority of the TEER sensor-based liver tumor MPS by its better anticancer activity based on cell viability and biomarker analysis compared to the traditional in vitro cell culture model. The anticancer effects of the plant extracts were successfully observed in real time, and methanolic extracts of Acer cappadocicum Gled increased the alanine transaminase and aspartate aminotransferase secretion, which may reveal the different mechanisms of these extracts and suggest a clue for the future molecular study of the anticancer pathways. Conclusion: Our results show that the liver tumor microphysiological system could be a better platform for plant-based anticancer activity assessment than traditional cell culture models.

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“… 36 The LAMPS system uses primary or iPSC hepatocytes and endothelial, Kupffer and stellate cells to create a device that replicates the multicellular components of the liver and was found to be a robust and reproducible method compared to traditional 2‐D monolayer cultures. 37 These devices are meant for low‐ to medium‐throughput investigations as they are labor intensive.…”

Section: Hepatic Mpsmentioning

confidence: 99%

Microphysiological systems in absorption, distribution, metabolism, and elimination sciences

Ness

Cesar

Yeung

et al. 2021

Clinical Translational Sci

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The use of microphysiological systems (MPS) to support Adsorption, Distribution, Metabolism, and Elimination (ADME) sciences has grown substantially in the last decade in part driven by regulatory demands to move away from traditional animal-based safety assessment studies and industry desires to develop methodologies to efficiently screen and characterize drugs in the development pipeline. The past decade of MPS development has yielded great user-driven technological advances with the collective fine-tuning of cell culture techniques, fluid delivery systems, materials engineering, and performance enhancing modifications.The rapid advances in MPS technology have now made it feasible to evaluate critical ADME parameters within a stand-alone organ system or through interconnected organ systems. This review surveys current MPS developed for liver, kidney, and intestinal systems as stand-alone or interconnected organ systems, and evaluates each system for specific performance criteria recommended by regulatory authorities and MPS leaders that would render each system suitable for evaluating drug ADME. While some systems are more suitable for ADME type research than others, not all system designs were intended to meet the recently published desired performance criteria and are reported as a summary of initial proof-of-concept studies. Liver-Intestinal chip Caco-2/ 383-1132  cm 2 No data CYP3A-triazolam No data Gut-liver chip Caco-2/HepaRG fluorescein Morphology: F-actin Apigeninsulfation and glucuronide conjugates No data Liver-gut MPS

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Analysis of reproducibility and robustness of a human microfluidic four-cell liver acinus microphysiology system (LAMPS)

Cited by 27 publications

References 49 publications

Quantifying the progression of non-alcoholic fatty liver disease in human biomimetic liver microphysiology systems with fluorescent protein biosensors

Quantifying the progression of non-alcoholic fatty liver disease in human biomimetic liver microphysiology systems with fluorescent protein biosensors

Study of the Anticancer Potential of Plant Extracts Using Liver Tumor Microphysiological System

Microphysiological systems in absorption, distribution, metabolism, and elimination sciences

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