Development of a living membrane comprising a functional human renal proximal tubule cell monolayer on polyethersulfone polymeric membrane

Schophuizen, Carolien M. S.; Napoli, Ilaria; Jansen, Jitske; Teixeira, Sérgio; Wilmer, Martijn J.; Hoenderop, Joost G. J.; Heuvel, L. P. W. van den; Masereeuw, Rosalinde; Stamatialis, Dimitrios

doi:10.1016/j.actbio.2014.12.002

Cited by 46 publications

(69 citation statements)

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“…Furthermore, to observe cell viability when grown on top of the hydrogels, a live/dead assay was carried out. Prior to cell seeding, all hydrogels were coated with l ‐DOPA to allow ciPTEC cell adhesion on the surface, as previously reported for other types of biomaterials . After 7 days of maturation, cells were stained with calcein‐AM and ethidium homodimer‐1 to distinguish live (green) from dead (red) cells.…”

Section: Resultsmentioning

confidence: 99%

“…For cell culture, round‐shaped pieces of the hydrogels (diameter 6 mm, thickness 0.85 mm, approximate surface growth area 0.28 cm 2 ) were cut out from compressed molded samples, sterilized with 0.2% v/v solution of peracetic acid (Sigma‐Aldrich, Zwijndrecht, the Netherlands) in 4% v/v ethanol for 45 min, and then extensively rinsed three times with HBSS and left in HBSS for additional 24 h. Afterward, small disks of hydrogels were introduced in empty wells of 96‐well plates and the l ‐DOPA ( l ‐3,4‐dihydroxyphenylalanine, Sigma‐Aldrich, Zwijndrecht, the Netherlands) coating was applied on the gels to support cell attachment and growth, based on previously published studies . l ‐DOPA was dissolved in 10 m m Tris buffer (pH 8.5) at 37 °C for 45 min with occasional mixing, filter sterilized, and applied on hydrogel surface at 2 mg mL −1 final concentration for 5 h at 37 °C, as described previously .…”

Section: Methodsmentioning

confidence: 99%

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Carbon Nanotube Reinforced Supramolecular Hydrogels for Bioapplications

Mihajlovic

Dankers

et al. 2018

Macromolecular Bioscience

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Nanocomposite hydrogels based on carbon nanotubes (CNTs) are known to possess remarkable stiffness, electrical, and thermal conductivity. However, they often make use of CNTs as fillers in covalently cross-linked hydrogel networks or involve direct cross-linking between CNTs and polymer chains, limiting processability properties. Herein, nanocomposite hydrogels are developed, in which CNTs are fillers in a physically cross-linked hydrogel. Supramolecular nanocomposites are prepared at various CNT concentrations, ranging from 0.5 to 6 wt%. Incorporation of 3 wt% of CNTs leads to an increase of the material's toughness by over 80%, and it enhances electrical conductivity by 358%, compared to CNT-free hydrogel. Meanwhile, the nanocomposite hydrogels maintain thixotropy and processability, typical of the parent hydrogel. The study also demonstrates that these materials display remarkable cytocompatibility and support cell growth and proliferation, while preserving their functional activities. These supramolecular nanocomposite hydrogels are therefore promising candidates for biomedical applications, in which both toughness and electrical conductivity are important parameters.

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Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Carbon Nanotube Reinforced Supramolecular Hydrogels for Bioapplications

Mihajlovic

Dankers

et al. 2018

Macromolecular Bioscience

Self Cite

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“…A number of 3D tissue engineering models have been developed that attempt to mimic the proximal tubule structure and function ((8, 16, 19, 20), for reviews see (5, 21)). A number of these systems utilize a monolayer of cells adhered to a microporous membrane coated with a thin layer of an ECM protein component, often collagen IV or laminin.…”

Section: Discussionmentioning

confidence: 99%

Development of a microphysiological model of human kidney proximal tubule function

Weber

Chapron

et al. 2016

Kidney International

219

218

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The kidney proximal tubule is the primary site in the nephron for excretion of waste products through a combination of active uptake and secretory processes, and is also a primary target of drug-induced nephrotoxicity. Here, we describe the development and functional characterization of a 3-dimensional flow-directed human kidney proximal tubule microphysiological system. The system replicates the polarity of the proximal tubule, expresses appropriate marker proteins, exhibits biochemical and synthetic activities, as well as secretory and reabsorptive processes associated with proximal tubule function in vivo. This microphysiological system can serve as an ideal platform for ex vivo modeling of renal drug clearance and drug-induced nephrotoxicity. Additionally, this novel system can be used for preclinical screening of new chemical compounds prior to initiating human clinical trials.

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“…Recently, a quintuple in vitro transporter model expressing OAT2/OCT2/OCT3/MATE1/ MATE2K was explored to evaluate the impact of test compounds on creatinine transport , but more data are needed to establish the predictive value of this model. Development and use of holistic models and integrated systems, such as immortalized cell lines derived from human kidney with preserved activity of transporters and drug-metabolizing enzymes, may provide more physiologically relevant models to study the interaction of drugs with the renal secretion of creatinine in the future (Schophuizen et al, 2015). Overall, a high variability of in vitro transporter inhibition data, not limited to OCT2/MATEs, has become a significant concern and may limit in vitro to in vivo extrapolation using universal cutoff values for transporter perpetrator decision trees, which trigger clinical DDI studies (Bentz et al, 2013).…”

Section: Discussionmentioning

confidence: 99%

The Complexities of Interpreting Reversible Elevated Serum Creatinine Levels in Drug Development: Does a Correlation with Inhibition of Renal Transporters Exist?

Chu

Bleasby

Chan

et al. 2016

Drug Metabolism and Disposition

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In humans, creatinine is formed by a multistep process in liver and muscle and eliminated via the kidney by a combination of glomerular filtration and active transport. Based on current evidence, creatinine can be taken up into renal proximal tubule cells by the basolaterally localized organic cation transporter 2 (OCT2) and the organic anion transporter 2, and effluxed into the urine by the apically localized multidrug and toxin extrusion protein 1 (MATE1) and MATE2K. Druginduced elevation of serum creatinine (SCr) and/or reduced creatinine renal clearance is routinely used as a marker for acute kidney injury. Interpretation of elevated SCr can be complex, because such increases can be reversible and explained by inhibition of renal transporters involved in active secretion of creatinine or other secondary factors, such as diet and disease state. Distinction between these possibilities is important from a drug development perspective, as increases in SCr can result in the termination of otherwise efficacious drug candidates. In this review, we discuss the challenges associated with using creatinine as a marker for kidney damage. Furthermore, to evaluate whether reversible changes in SCr can be predicted prospectively based on in vitro transporter inhibition data, an in-depth in vitro-in vivo correlation (IVIVC) analysis was conducted for 16 drugs with in-house and literature in vitro transporter inhibition data for OCT2, MATE1, and MATE2K, as well as total and unbound maximum plasma concentration (C max and C max,u ) data measured in the clinic.

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Development of a living membrane comprising a functional human renal proximal tubule cell monolayer on polyethersulfone polymeric membrane

Cited by 46 publications

References 50 publications

Carbon Nanotube Reinforced Supramolecular Hydrogels for Bioapplications

Carbon Nanotube Reinforced Supramolecular Hydrogels for Bioapplications

Development of a microphysiological model of human kidney proximal tubule function

The Complexities of Interpreting Reversible Elevated Serum Creatinine Levels in Drug Development: Does a Correlation with Inhibition of Renal Transporters Exist?

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