Toxicological Effects of Titanium Dioxide Nanoparticles on Human Menstrual Blood Mesenchymal Stem Cells

Human exposure to titanium dioxide nanoparticles (TiO₂ NPs) is common. These NPs are used in cosmetics, paint, food, and other products. Their nanometric size (<100 nm) allows entry into the bloodstream, from which they can reach organs and cells throughout the body. Although TiO₂ NPs have been reported to damage certain cell lines and organs and to alter cellular function, their impact on human menstrual blood mesenchymal stem cells (hMB-MSCs) is unknown. This study evaluated the effects of TiO₂ NPs on viability, proliferation, morphology, membrane-marker expression, and reactive oxygen species (ROS) production in primary cultures of hMB-MSCs derived from menstrual blood. Cells were exposed to different concentrations of TiO₂ NPs for 3, 7, and 14 days. TiO₂ NPs decreased hMB-MSC viability and proliferation in a concentration- and time-dependent manner. Cellular viability was reduced by up to 6%, 11%, and 18% at 3, 7, and 14 days, respectively (statistically significant vs. control). Cellular proliferation decreased by 3%, 5%, and 33% at 15.63, 62.5, and 250 μg/mL TiO₂, respectively. TiO₂ NPs were internalized and observed in the cytoplasm, forming perinuclear aggregates. NP-exposed cells showed reduced membrane expression of CD73 (7.9% decrease) and CD90 (25.72% decrease) compared with control cells. Finally, TiO₂ NPs at 15.63, 62.5, and 250 µg/mL reduced ROS generation by 56.79%, 62.79%, and 53.35%, respectively, after 4 h (statistically significant vs. control). In summary, exposure to high concentrations of TiO₂ NPs leads to intracellular nanoparticle deposits and alters key functions of human menstrual blood mesenchymal stem cells, including immunomodulation, immune protection, molecular behavior, cell differentiation, and regenerative capacity.