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Abstract Nephrotoxicity is a significant concern during the development of new drugs or when assessing the safety of chemicals in consumer products. Traditional methods for testing nephrotoxicity involve animal models or 2D in vitro cell cultures, the latter of which lack the complexity and functionality of the human kidney. 3D in vitro models are created by culturing human primary kidney cells derived from urine in a 3D microenvironment that mimics the fluid shear stresses of the kidney. Thus, 3D in vitro models provide more accurate and reliable predictions of human nephrotoxicity compared to existing 2D models. In this review, we focus on precision nephrotoxicity testing using 3D in vitro models with human autologous urine-derived kidney cells as a promising approach for evaluating drug safety.

Endothelial cells (ECs) play a key role in revascularization within regenerating tissue. Stem cells are often used as an alternative cell source when ECs are not available. Several cell types have been used to give rise to ECs, such as umbilical cord vessels, or differentiated from somatic stem cells, embryonic, or induced pluripotent stem cells. However, the latter carry the potential risk of chronic immune rejection and oncogenesis. Autologous endothelial precursors are an ideal resource, but currently require an invasive procedure to obtain them from the patient's own blood vessels or bone marrow. Thus, the goal of this study was to determine whether urine-derived stem cells (USCs) could differentiate into functional ECs in vitro. Urine-derived cells were then differentiated into cells of the endothelial lineage using endothelial differentiation medium for 14 days. Changes in morphology and ultrastructure, and functional endothelial marker expression were assessed in the induced USCs in vitro. Grafts of the differentiated USCs were then subcutaneously injected into nude mice. Induced USCs expressed significantly higher levels of specific markers of ECs (CD31, vWF, eNOS) in vitro and in vivo, compared to nondifferentiated USCs. In addition, the differentiated USC formed intricate tubular networks and presented similar tight junctions, and migration and invasion ability, as well as ability to produce nitric oxide (NO) compared to controls. Using USCs as autologous EC sources for vessel, tissue engineering strategies can yield a sufficient number of cells via a noninvasive, simple, and low-cost method suitable for rapid clinical translation. Stem Cells Translational Medicine 2018 Stem Cells Translational Medicine 2018;7:686-698., (© 2018 The Authors Stem Cells Translational Medicine published by Wiley Periodicals, Inc. on behalf of AlphaMed Press.)