Introduction: Glioblastoma is the most common, invasive, and deadliest of all primary brain tumors and accounts for 45.2% of malignant tumors of the central nervous system.
Poor prognosis reduces the likelihood of these patients recovering and increases their risk of death. The one-year survival rate of these patients is reported to be 35%.
The first step in treating patients with glioblastoma is the surgical removal of the tumor. Use of temozolomide chemotherapy in addition to common treatments such as surgery and resection. Tumor and radiation therapy have increased patients' life expectancy, but only 5% of patients survive after initial diagnosis.
One of the reasons for the low success of common treatments for this tumor is the inherent resistance of the tumor to chemotherapy and radiotherapy. Also, complete surgery of the tumor is not possible due to the special position and aggressive nature of the tumor, the presence of the blood-brain barrier, cancer stem cells, and tumor heterogeneity are other reasons for the difficult treatment of this disease. Therefore, new therapeutic strategies to target and kill glioblastoma cells need to greatly increase the effectiveness of treatment.
One of the targeted therapies for this disease is gene therapy, which to some extent overcomes the mentioned therapeutic challenges, especially low tumor blood flow, and blood-brain barrier.
There are currently four types of potential gene therapy in GBMI therapy: Suicide genes, which cause the local production of toxic compounds; Immune-mediating genes, which enhance or enhance the anti-tumor immune response; Tumor suppressor genes, which induce apoptosis in cancer cells; and treatment with oncolytic viruses, which lysis tumor cells and deliver a variety of therapeutic genes.
It is now important to design safe vectors with long-term gene expression, as well as to develop a highly specific method for identifying gene therapy target cells and regulating the expression of those genes by micromolecules.
Delivery systems include direct gene delivery (viral and non-viral vectors such as liposomes, micelles, and nanoparticles), tumor-oriented cell carriers, and intelligent carriers.
One of the carriers of gene therapy is stem cells, which we will discuss in this article.
The most important limitation of the presentation of genes by viral vectors is that they are not able to infect all cancer cells, but stem cells do not. Neuronal stem cells, mesenchymal stem cells, and induced pluripotent cells are three suitable candidates for vector gene therapy.
Methods: Publications were retrieved by a systemic search of multiple bibliographic databases, including Medline, Embase, Scopus, Biomed central, PubMed and google scholar. The search was narrowed to the original articles published in English from2019 to 2021.
Results: Neuronal stem cells have a natural tendency towards brain tumor tissue. The tumorigenic capabilities of NSCs and their ability to stably express the presented genes make them ideal cell carriers. Another interesting aspect of NSCs is that they can be delivered to the skull not only through systemic injections but also through an intranasal route.
Empirically, NSCs contain a variety of genes and are successfully delivered to the tumor site. For example, in combination with oncolytic adenoviruses in the in vivo test, they effectively target the tumor and reduce tumor growth. NSCs are also designed to transport cytokines, nanoparticles, and enzymes to convert ineffective prodrugs to chemotherapeutic drugs.
Mesenchymal stem cells are relatively easy to separate from NSCs and can be obtained autologous from the bone marrow and manipulated back into the same patient. As a result, they prevent an allogeneic response in the carrier. MSCs are also designed to express TRAIL and CD with strong antitumor effects.
Another type of cellular carrier is iPSCs. The benefits of using iPSCs instead of stem cells include their ability to escape rejection by the immune system and the absence of ethical concerns when using human embryonic cells. In addition, iPSCs can be easily manufactured from somatic cells, making them an ideal choice for research on many model systems.
Conclusion: The ineffectiveness of common therapies in the most invasive brain tumors opens a new window for targeted therapies. The effectiveness of current glioblastoma treatments can be enhanced by more effective and designed methods. New smart carrier design strategies in combination with conventional therapies, will be a hope for increasing the survival of these patients.
Keywords: Glioblastoma, Stem cells, Gene therapy, Drug delivery, Drug carriers