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.

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Aplastic anemia (AA) is a rare and serious disorder of hematopoietic stem cells (HSCs) that results in the loss of blood cells due to the failure of the bone marrow (BM). Although BM transplantation is used to treat AA, its use is limited by donor availability. In this sense, mesenchymal stem cells (MSCs) can offer a novel therapeutic approach for AA. This is because the MSCs contribute to the hematopoietic niche organization through their repopulating. In our study, we used the human immature dental pulp stem cell (hIDPSC), an MSC-like cell, to explore an alternative therapeutic approach for AA. For this, isogenic C57BL/6 mice were exposed to total body irradiation (TBI) to induce the AA. After 48 h of TBI, the mice were intraperitoneally treated with hIDPSC. The immunohistochemistry analyses confirmed that the hIDPSCs migrated and grafted in the mouse bone marrow (BM) and spleen, providing rapid support to hematopoiesis recovery compared to the group exposed to radiation, but not to those treated with the cells as well as the hematological parameters. Six months after the last hIDPSC transplantation, the BM showed long-term stable hematopoiesis. Our data highlight the therapeutic plasticity and hematoprotective role of hIDPSC for AA and potentially for other hematopoietic failures.

Background: Although the safety of mesenchymal stroma/stem cells (MSCs)-based therapies had already extensively demonstrated, non-clinical biodistribution studies are essential for predicting the safety and efficacy of these cells. Herein we assessed the biodistribution of human immature dental pulp stem cells (hIDPSCs), which has investigated as a candidate for the treatment of Huntington’s disease (HD). Method: For this, we intravenously transplanted hIDPSCs transfected with luciferase or labeled with magnetic nanoparticle in C57BL/6 mice and performed the bioluminescence image (BLI) or inductively coupled plasma mass spectrometer (ICP-MS) to quantity in vivo and ex vivo biodistribution after 4h, 24h, 3, 7, and 30 days of the hIDPSCs administration. Results: BLI’s results showed the presence of hIDPSCs in the chest, lungs, and head after 4h, 24 h, and 3 days of the cell transplantation. No bioluminescent signal was observed in the chest or head on days 7 and 30 days. The ICP-MS’s results showed that the hIDPSCs engraft into the liver, kidney, heart, and lungs. However, the number of hIDPSCs in these sites significantly reduced from the seventh day, being undetectable on the 30th day. By contrast, we observed that the hIDPSCs not only engrafted into the brain, but also remain in this organ for 30 days. Conclusion: These data provide evidence that the hIDPSCs successfully engraft and remain in the brain for until 30 days after the cell transplantation, demonstrating that these cells can migrate and homing to the brain, being a useful candidate for the treatment of neurodegenerative disorders, such as HD.

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