Cancer comprises a group of heterogeneous diseases encompassing high rates of morbidity and mortality. Heterogeneity, which is a hallmark of cancer, is one of the main factors related to resistance to chemotherapeutic agents leading to poor prognosis. Heterogeneity is profoundly affected by increasing levels of ROS. Under low concentrations, ROS may function as signaling molecules favoring tumorigenesis and heterogeneity, while under high ROS concentrations, these species may work as cancer modulators due to their deleterious, genotoxic or even proapoptotic effect on cancer cells. This double‐edged sword effect represented by ROS relies on their ability to cause genetic and epigenetic modifications in DNA structure. Antitumor therapeutic approaches may use molecules that prevent the ROS formation precluding carcinogenesis or use chemical agents that promote a sudden increase of ROS causing considerable oxidative stress inside tumor mass. Therefore, herein, we review what ROS are and how they are produced in normal and in cancer cells while providing an argumentative discussion about their role in cancer pathophysiology. We also describe the various sources of ROS in cancer and their role in tumor heterogeneity. Further, we also discuss some therapeutic strategies from the current landscape of cancer heterogeneity, ROS modulation, or ROS production.

Cancer is one of the most important health problems and the second leading cause of death worldwide. Despite the advances in oncology, cancer heterogeneity remains challenging to therapeutics. This is because the exosome-mediated crosstalk between cancer and non-cancer cells within the tumor microenvironment (TME) contributes to the acquisition of all hallmarks of cancer and leads to the formation of cancer stem cells (CSCs), which exhibit resistance to a range of anticancer drugs. Thus, this review aims to summarize the role of TME-derived exosomes in cancer biology and explore the clinical potential of mesenchymal stem-cell-derived exosomes as a cancer treatment, discussing future prospects of cell-free therapy for cancer treatment and challenges to be overcome.

The aging population has contributed to the rapid rise in the global incidence of neurodegenerative diseases. Despite the medical advances, there are no effective treatments for these disorders. Therefore, there is an urgent need for new treatments for these diseases. In this sense, cell therapy has been recognized as the best candidate for treating incurable diseases, such as neurodegenerative disorders. However, the therapeutic use of these cells can be limited by several factors. Thus, there has been a rediscovery that extracellular vesicles, including exosomes, can be alternatively explored in the treatment of these diseases, overcoming the limits of cell-based therapy. In this sense, this review aims to revisit all areas from biology, including biogenesis and the content of exosomes, to biotechnology, proposing the minimal information required to isolate, characterize, and study the content of these vesicles for scientific and/or clinical purposes.

Huntington’s disease (HD) is a neurodegenerative inherited genetic disorder, which leads to the onset of motor, neuropsychiatric and cognitive disturbances. HD is characterized by the loss of gamma-aminobutyric acid (GABA)ergic medium spiny neurons (MSNs). To date, there is no treatment for HD. Mesenchymal stem cells (MSCs) provide a substantial therapeutic opportunity for the HD treatment. Herein, we investigated the therapeutic potential of human immature dental pulp stem cells (hIDPSC), a special type of MSC originated from the neural crest, for HD treatment. Two different doses of hIDPSC were intravenously administrated in a subacute 3-nitropropionic acid (3NP)-induced rat model. We demonstrated hIDPSC homing in the striatum, cortex and subventricular zone using specific markers for human cells. Thirty days after hIDPSC administration, the cells found in the brain are still express hallmarks of undifferentiated MSC. Immunohistochemistry quantities analysis revealed a significant increase in the number of BDNF, DARPP32 and D2R positive stained cells in the striatum and cortex in the groups that received hIDPSC. The differences were more expressive in animals that received only one administration of hIDPSC. Altogether, these data suggest that the intravenous administration of hIDPSCs can restore the BDNF, DARPP32 and D2R expression, promoting neuroprotection and neurogenesis.