Synthetic biomaterials as coatings for kidney tissue engineering applications
Mohammed Shahrudin Ibrahim
Date of Issue2018-09-05
School of Chemical and Biomedical Engineering
Poorly-defined animal-derived extracellular matrices (ECMs) used as substrates for pluripotent stem cell expansion and differentiation are expensive, suffer from batch to batch variations, and have low relevance with respect to clinical applications. Recently, our lab has synthesized two types of synthetic chemically-defined nanoparticles, NP1 and NP2 respectively, that were able to support the expansion of pluripotent stem cells for up to 23 passages [Erathodiyil et al., unpublished results]. Herein, we show that these synthetic substrates can effectively support the differentiation of induced pluripotent stem cells (iPSCs) into human primary renal proximal tubule cell (HPTC)-like cells with a similar efficiency as Matrigel. The resultant HPTC-like cells differentiated on NP2 expressed similar or higher levels of proximal tubule cell (PTC) markers SLC34A1 (1.65-fold), PEPT1 (8.43-fold), AQP1 (6.23-fold), CD13 (10.02-fold), GGT (3.93-fold), VITD3 (2.27-fold), NBC1 (4.16-fold), SGLT2 (5.60-fold) and GLUT5 (7.35-fold) in comparison to cells differentiated on Matrigel. However, elevated levels of mesenchymal markers and markers expressed by other renal cell types were also observed. Fluorescence-activated cell sorting (FACS) analysis revealed that HPTC-like cells differentiated on NP2 substrates have a high percentage of cells positive for PTC markers PEPT1, OAT3, AQP1, URO10 and GLUT1. Results obtained by compound screening suggested that HPTC-like cells obtained on NP2 would be a suitable in vitro cell model for screening of PTC-specific nephrotoxicants.