(−)-Epicatechin (EC), a bioactive compound found in the plant kingdom contained in beans from the cacao tree, and other vegetables, has high flavonoid content. Traditionally consumed as chocolate, presents various benefits in human health. Many flavonoids have demonstrated therapeutic effects against osteoporosis by enhancing bone density; however, the specific impact of EC on bone regeneration remains unknown. Since bone regeneration involves a small group of responsive stem cells, we investigated the flavonoids’ effects on key bone precursors like mesenchymal stem cells (MSCs). We used a conventional osteogenic medium alone or combined with different EC concentrations. Our study revealed that low concentrations of EC could enhance the expression of osteogenic genes when combined with low concentrations of osteogenic medium and induced the highest differentiation of human MSCs compared with pharmacological concentrations. So, the increase in the expression of osteoblastic marker genes such as bone morphogenetic protein 2, Runt-related transcription factor 2, and secreted protein acidic and cysteine rich agreed with an increase in cellular calcium deposits. Therefore, we conclude that the natural flavonol (−)-EC improved the expression of genes involved in bone regeneration and could potentially serve as an adjunctive therapy for bone loss diseases.

Mesenchymal stem cell (MSC) treatments take advantage of the ability of these cells to migrate to target sites, although they have been shown to move in response to tumor influence. Currently, tools are being developed to detect these opportune changes in cellular behavior patterns. No reports of such changes in the morphological patterns or migration of MSCs in the presence of a tumor environment, which would provide information of high diagnostic value, have been made. We determined the changes in the cytoskeleton and migration of MSCs exposed to the secretome of breast tumor cells via bioimpedance records. MSCs were cultured and incubated in the presence of 24 and 48 h secretomes of the MCF-7 tumor cell line. The proliferation, migration, morphology, cytoskeleton, and electrical bioimpedance were evaluated at 48 h for cells treated with 24 and 48 h secretomes. Secretomes induced early morphological changes related to the migration of MSCs, directly confirmed via bioimpedance, but no changes in cell proliferation were found. These changes cannot be related to a transformation or malignancy phenotype. The modification of the bioimpedance patterns recorded from the first hours suggests that this method can be applied in an innovative way to detect early changes in a cellular population in the clinical diagnostic setting.

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.

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.