Efficient proximal tubule-on-chip model from hiPSC-derived kidney organoids for functional analysis of renal transporters.

ABSTRACT: Renal transporters play critical roles in predicting potential drug-drug interactions. However, current in vitro models often fail to adequately express these transporters, particularly solute carrier proteins, including organic anion transporters (OAT1/3), and organic cation transporter 2 (OCT2). Here, we developed a hiPSC-derived kidney organoids-based proximal tubule-on-chip (OPTC) model that emulates in vivo renal physiology to assess transporter function. Compared to chips based on immortalized cells, OPTC derived from the two most commonly used differentiation protocols exhibited significant improvement in expression level and polarity of OAT1/3 and OCT2. Hence, the OPTC demonstrates enhanced functionality in efflux and uptake assessments, and nephrotoxicity. Furthermor

SUBMITTER: Ma C 

PROVIDER: S-EPMC11403423 | biostudies-literature | 2024 Sep

REPOSITORIES: biostudies-literature