Introduction: The tumor microenvironment (TME) consists of different types of cells and an extracellular matrix, of which mesenchymal stem cells (MSCs) are part of this microenvironment. Previous studies have shown that various factors in the TME including mesenchymal stem cells known as cancer-associated stem cells (CA-MSCs), cause low efficacy of immunotherapy, tumor progression, and relapse. These cells cause tumor cell growth, metastasis, angiogenesis, immune system escape, and drug resistance in the tumor environment. However, MSCs, MSC-derived membranes and MSC-derived exosomes can be used as carriers of chemotherapy drugs, oncolytic viruses, or therapeutic genes to precisely deliver cytotoxic agents to cancer sites. Therefore, MSCs can be considered as a promising source in tumor treatment.
Methods: Mesenchymal stem cells (MSCs), one of the most widespread cells in the human body, were first discovered in 1976 (1). In general, MSCs are known as pluripotent stem cells that can differentiate into adipocytes, chondrocytes, osteocytes, and other lineages (2). Also, they can adhere to plastic containers and multiply in laboratory conditions. These cells express CD73, CD90, and CD105 on their surface, but lack CD14, CD45, CD19, and HLA-DR. In addition to modulating the immune system, MSCs also repair damaged tissue. They migrate to the tissue through the chemokines that are released from the damaged tissue, and by differentiating into tissue-specific mature cells, they repair the damaged tissue (3).
Today, cancer is known as the most common and deadly disease. Also, the role of MSCs in the initiation, growth, and metastasis of cancer has been proven (4). MSCs found in tumor tissue are called tumor-associated mesenchymal stem cells (TA-MSCs). Many studies have shown that TA-MSCs play a tumor-promoting role (5–7). But today, it has been shown that MSCs can have an anti-tumor effect despite the stimulating impact on tumor growth (8–10). Therefore, we decided to review the discoveries regarding MSC-based anticancer therapy.
Results: Review
Conclusion: Today, using MSCs for cancer treatment is one of the emerging attractive treatment options. TA-MSC cells in TME can affect tumor cells through direct cell-to-cell contact, MSC-derived exosomes and cytokines, or signaling pathways. According to recent studies, researchers believe that TA-MSC can be one of the main culprits in tumor progression. Therefore, tumor progression can be prevented by inhibiting the proliferation of TA-MSCs. 1) Reduction of factors effective in angiogenesis and proliferation that are released from MSC, 2) Inhibiting the release of chemokines that play a role in the tropism of MSCs to the tumor environment, and 3) Suppression of factors that cause drug resistance in tumor cells in combination with oncotherapy, can inhibit the development of tumor cells. MSCs containing anti-tumor drugs, oncolytic viruses, and suicide genes can also be used for tumor treatment by genetic engineering. Therefore, whether to use MSC as a therapeutic target or as a tool for tumor treatment is still debated.