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.

Diabetic foot ulcers (DFUs) represent 6.3% of the various complications of type 2 diabetes mellitus, with a risk of development of up to 34%. Several factors contribute to the formation of ulcers, which are very difficult to treat as they hinder efficient wound healing. Patients experience persistent pain, which leads to the consumption of various medications (polypharmacy) due to the lesions not resolving. Conversely, this can increase the risk of various factors, including a chronic inflammatory state, which hinders the body’s own regenerative processes. Until now, treatment options have been limited to washing the wound and stimulating new tissue growth, but this is a painful and unsuccessful process. One of the treatment options is therefore cell therapy with mesenchymal stem cells, which have immunomodulatory characteristics and allow tissue regeneration, although the effect directly in pain is not totally clear. We have previously reported in our working group that patients with ulcers treated with mesenchymal stem cells (MSCs) have been able to integrate into their daily lives, although the pain related to the inflammatory state and polypharmacy has not been studied. Objective: This study investigates how the local administration of MSCs improves the condition of an ulcer by inducing tissue regeneration. It also shows how the concentration of systemic inflammatory biomarkers is modified in direct correlation with pain and the consumption of medications over time. Methods: Local administration of MSCs at 7 and 14 days, measuring pro- and anti-inflammatory cytokines relative to the healthy control group, evaluating wound healing, and monitoring the medications taken by the patient in conjunction with pain perception. Results: Cell administration showed that inflammatory molecules were reduced and anti-inflammatory molecules increased. This is reflected in the consumption of Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) in relation to wound improvement, with a decrease in pain medication consumption of less than 50%. We provide evidence that locally administered mesenchymal stem cells influence systemic inflammatory processes necessary for tissue recovery, impacting patients’ polypharmacy consumption due to reduced perceived pain. Conclusions: This report establishes a direct link between mesenchymal stem cells and pain relief in type 2 diabetes ulcers, potentially paving the way for new pain therapies.

In this chapter, we described various aspects related to the role of molecules involved in redox balance and their involvement in the development of neoplasms. In normal cells, oxidative stress is typically maintained at moderate levels to balance reactive oxygen species within a functional dynamic range; however, tumor cells develop a highly structured system that allows them to sustain survival, proliferation, invasion, and chemoresistance by altering the fate of cell proliferation. Thus, when reactive oxygen species reach high concentrations, they can exert an antioncogenic effect by inducing apoptosis and inhibiting cell proliferation. In this sense, free radicals produced during tumor development play a dual role in cancer, which can either promote tumor progression or, under certain conditions, become a potential tool for the elimination of malignant cells.