Characterization of Organic Anion and Cation Transport in Three Human Renal Proximal Tubular Epithelial Models

• Published in: Cells (Basel, Switzerland) Vol. 13; no. 12; p. 1008
• Main Authors: Meijer, Tamara, da Costa Pereira, Daniel, Klatt, Olivia C, Buitenhuis, Joanne, Jennings, Paul, Wilmes, Anja
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 09-06-2024; MDPI
• Subjects: Anions - metabolism; Biological Transport; Cations - metabolism; Cell culture; Cell differentiation; Cell Line; Collagen; Computers; Epidermal growth factor; Epithelial cells; Epithelial Cells - metabolism; Ethylenediaminetetraacetic acid; Fluoresceins - metabolism; human induced pluripotent stem cells; Humans; Induced Pluripotent Stem Cells - cytology; Induced Pluripotent Stem Cells - metabolism; Kidney diseases; Kidney Tubules, Proximal - cytology; Kidney Tubules, Proximal - metabolism; Kidneys; Models, Biological; organic anion transport; Organic Anion Transporters - genetics; Organic Anion Transporters - metabolism; organic cation transport; Organic Cation Transport Proteins - genetics; Organic Cation Transport Proteins - metabolism; Permeability; Pluripotency; Polyethylene terephthalate; Proteins; Pyridinium Compounds - metabolism; Quinidine; renal proximal tubule; Services; Stem cells; Telomerase; Toxicity; Netherlands; United States > US; human induced pluripotent stem cells; organic anion transport; renal proximal tubule; organic cation transport
• ISSN: 2073-4409; 2073-4409
• DOI: 10.3390/cells13121008

The polarised expression of specific transporters in proximal tubular epithelial cells is important for the renal clearance of many endogenous and exogenous compounds. Thus, ideally, the in vitro tools utilised for predictions would have a similar expression of apical and basolateral xenobiotic transporters as in vivo. Here, we assessed the functionality of organic cation and anion transporters in proximal tubular-like cells (PTL) differentiated from human induced pluripotent stem cells (iPSC), primary human proximal tubular epithelial cells (PTEC), and telomerase-immortalised human renal proximal tubular epithelial cells (RPTEC/TERT1). Organic cation and anion transport were studied using the fluorescent substrates 4-(4-(dimethylamino)styryl)-N-methylpyridinium iodide (ASP) and 6-carboxyfluorescein (6-CF), respectively. The level and rate of intracellular ASP accumulation in PTL following basolateral application were slightly lower but within a 3-fold range compared to primary PTEC and RPTEC/TERT1 cells. The basolateral uptake of ASP and its subsequent apical efflux could be inhibited by basolateral exposure to quinidine in all models. Of the three models, only PTL showed a modest preferential basolateral-to-apical 6-CF transfer. These results show that organic cation transport could be demonstrated in all three models, but more research is needed to improve and optimise organic anion transporter expression and functionality.