Summary
Published in Pharmaceutics (2022), this peer-reviewed study used 3D Petri Dish® micro-molds to form scaffold-free 3D microtissues. Full citation: Ding, Huifen, et al. 3D Spheroids of Human Primary Urine-Derived Stem Cells in the Assessment of Drug-Induced Mitochondrial Toxicity
3D Spheroids of Human Primary Urine-Derived Stem Cells in the Assessment of Drug-Induced Mitochondrial Toxicity
Research Overview
No in vitro assay existed to test long-term mitochondrial toxicity — four weeks or more — even though delayed toxicity is a real clinical risk. This study developed a 3D spheroid system of human primary urine-derived stem cells to predict drug-induced delayed mitochondrial toxicity.
Spheroids were assessed four weeks after treatment with the antiretrovirals zalcitabine, tenofovir, or raltegravir across three concentrations each, with rotenone and DMSO as controls. Despite only mild cytotoxicity, zalcitabine significantly inhibited oxidative-phosphorylation Complexes I, III, and IV, and raltegravir transiently reduced Complex IV. Caspase-3 and reactive oxygen and nitrogen species rose while total ATP fell in cells treated with all three drugs and rotenone.
Key Discoveries
- Urine-derived stem cell spheroids enabled 4-week mitochondrial toxicity testing of antiretrovirals
- Zalcitabine inhibited Complexes I, III, and IV despite only mild cytotoxicity; raltegravir transiently reduced Complex IV
- Caspase-3 and ROS/RNS increased while total ATP decreased across the tested drugs
