Predicting tubular reabsorption with a human kidney proximal tubule tissue-on-a-chip and physiologically-based modeling

Sakolish, Courtney; Chen, Zunwei; Dalaijamts, Chimeddulam; Mitra, Kusumica; Liu, Yina; Fulton, Tracy B.; Wade, Terry L.; Kelly, Edward J.; Rusyn, Ivan; Chiu, Weihsueh A.

doi:10.1016/j.tiv.2019.104752

Cited by 35 publications

(36 citation statements)

References 69 publications

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“…12 A useful prioritization of MPS applications can be found in Table 1 of the review by Watson, Hunziker, and Wikswo, 2017. 10 Currently, there are MPS of nearly every major human organ 20 including liver, 16,41 vasculature, 42,43 blood-brain barrier (BBB), [44][45][46] skeletal [47][48][49] and cardiac muscle, [50][51][52][53][54][55][56][57] kidney, [58][59][60][61] female reproductive tissues (uterus, cervix, fallopian tubes), 62 testes, 63 brain, 37,64 skin, [65][66][67] gut, 40 bone, 68 and eye. 69,70 Specific MPS organ systems have also been linked to form multi-organ systems to more accurately depict systemic responses to a variety of drugs and therapeutics.…”

Section: Impact Statementmentioning

confidence: 99%

“…12 Ultimately, this 5-year program provided proof of principle that tissue chips could accurately recapitulate human physiology and drug responses. 12 While DARPA funding ended in 2017, the NIH MPS program has continued and since evolved to look at various tissue chip technology end uses, including disease modeling and efficacy testing; [74][75][76][77][78][79] modeling opioid use disorders; using tissue chips to improve clinical trial design and execution; and creating independent validation/testing centers 59,[80][81][82] plus a publicly accessible database 83,84 for MPS data. In addition to the NIH and DARPA MPS programs, the US Environmental Protection Agency established the "Science to Achieve Results" (STAR) grant program, one goal of which is to further the development of organotypic culture models, including organs-on-chips (OoCs) for predictive toxicology.…”

Section: Impact Statementmentioning

confidence: 99%

“…A recent case study by one of these centers investigating a human kidney proximal tubule tissue chip revealed that overall reproducibility in data is greatly dependent on the cell source. 59,80 The source, cell types, and microenvironment of cellular materials used within MPS devices are therefore of great importance. Various cell types are currently being used including primary cells, immortalized cell lines, and human pluripotent stem cells.…”

Section: Cell Types Used In Microphysiological Systemsmentioning

confidence: 99%

“…8 These Testing Centers collaborate with the FDA and pharmaceutical industry partners to validate assays and outcomes from MPS platform developers, and a variety of platforms have been tested to date. 59,80,87,138 Data collected from both developers and the Testing Centers are deposited into a central, publicly accessible MPS Database, where users are able to access assay data as well as compare chip data with preclinical data from other modalities 83,84 (Figure 2). In addition to these validation efforts, the Tissue Chips in Space Program are working to develop robust automated MPS platforms with small laboratory benchtop footprints.…”

Section: Multi-organ Mps Platform Integrationmentioning

confidence: 99%

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Microphysiological systems: What it takes for community adoption

Hargrove-Grimes

Low

Tagle

2021

Exp Biol Med (Maywood)

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Microphysiological systems (MPS) are promising in vitro tools which could substantially improve the drug development process, particularly for underserved patient populations such as those with rare diseases, neural disorders, and diseases impacting pediatric populations. Currently, one of the major goals of the National Institutes of Health MPS program, led by the National Center for Advancing Translational Sciences (NCATS), is to demonstrate the utility of this emerging technology and help support the path to community adoption. However, community adoption of MPS technology has been hindered by a variety of factors including biological and technological challenges in device creation, issues with validation and standardization of MPS technology, and potential complications related to commercialization. In this brief Minireview, we offer an NCATS perspective on what current barriers exist to MPS adoption and provide an outlook on the future path to adoption of these in vitro tools.

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Section: Impact Statementmentioning

confidence: 99%

Section: Impact Statementmentioning

confidence: 99%

Section: Cell Types Used In Microphysiological Systemsmentioning

confidence: 99%

Section: Multi-organ Mps Platform Integrationmentioning

confidence: 99%

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Microphysiological systems: What it takes for community adoption

Hargrove-Grimes

Low

Tagle

2021

Exp Biol Med (Maywood)

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“…Experimental data derived from MPS, in combination with mathematical in silico modeling has enormous potential to accelerate drug development. Sakolish et al combined PTEC MPS data with PBPK models for polymyxin B, cisplatin, and gentamicin to reproduce renal reabsorption kinetics and predict renal clearance in vivo ( Sakolish et al, 2020 ). In a complimentary study, Maass et al paired a kidney MPS with a computational quantitative systems pharmacology (QSP) model to assess drug-induced renal toxicity.…”

Section: Introductionmentioning

confidence: 99%

Kidney Organoid and Microphysiological Kidney Chip Models to Accelerate Drug Development and Reduce Animal Testing

et al. 2021

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Kidneys are critical for the elimination of many drugs and metabolites via the urine, filtering waste and maintaining proper fluid and electrolyte balance. Emerging technologies incorporating engineered three-dimensional (3D) in vitro cell culture models, such as organoids and microphysiological systems (MPS) culture platforms, have been developed to replicate nephron function, leading to enhanced efficacy, safety, and toxicity evaluation of new drugs and environmental exposures. Organoids are tiny, self-organized three-dimensional tissue cultures derived from stem cells that can include dozens of cell types to replicate the complexity of an organ. In contrast, MPS are highly controlled fluidic culture systems consisting of isolated cell type(s) that can be used to deconvolute mechanism and pathophysiology. Both systems, having their own unique benefits and disadvantages, have exciting applications in the field of kidney disease modeling and therapeutic discovery and toxicology. In this review, we discuss current uses of both hPSC-derived organoids and MPS as pre-clinical models for studying kidney diseases and drug induced nephrotoxicity. Examples such as the use of organoids to model autosomal dominant polycystic kidney disease, and the use of MPS to predict renal clearance and nephrotoxic concentrations of novel drugs are briefly discussed. Taken together, these novel platforms allow investigators to elaborate critical scientific questions. While much work needs to be done, utility of these 3D cell culture technologies has an optimistic outlook and the potential to accelerate drug development while reducing the use of animal testing.

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Emerging tissue engineering strategies for the corneal regeneration

Tafti

Aghamollaei

Moghaddam

et al. 2022

J Tissue Eng Regen Med

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Cornea as the outermost layer of the eye is at risk of various genetic and environmental diseases that can damage the cornea and impair vision. Corneal transplantation is among the most applicable surgical procedures for repairing the defected tissue. However, the scarcity of healthy tissue donations as well as transplantation failure has remained as the biggest challenges in confront of corneal grafting. Therefore, alternative approaches based on stem-cell transplantation and classic regenerative medicine have been developed for corneal regeneration. In this review, the application and limitation of the recently-used advanced approaches for regeneration of cornea are discussed. Additionally, other emerging powerful techniques such as 5D printing as a new branch of scaffold-based technologies for construction of tissues other than the cornea are highlighted and suggested as alternatives for corneal reconstruction. The introduced novel techniques may have great potential for clinical applications in corneal repair including disease modeling, 3D pattern scheming, and personalized medicine.

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Predicting tubular reabsorption with a human kidney proximal tubule tissue-on-a-chip and physiologically-based modeling

Cited by 35 publications

References 69 publications

Microphysiological systems: What it takes for community adoption

Microphysiological systems: What it takes for community adoption

Kidney Organoid and Microphysiological Kidney Chip Models to Accelerate Drug Development and Reduce Animal Testing

Emerging tissue engineering strategies for the corneal regeneration

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