Mesenchymal stem cells: A new platform for targeting suicide genes in cancer

Abstract

One of the important strategies for the treatment of cancer is gene therapy which has the potential to exclusively eradicate malignant cells, without any damage to the normal tissues. Gene-directed enzyme prodrug therapy (GDEPT) is a two-step gene therapy approach, where a suicide gene is directed to tumor cells. The gene encodes an enzyme that expressed intracellularly where it is able to convert a prodrug into cytotoxic metabolites. Various delivery systems have been developed to achieve the appropriate levels of tumor restricted expression of chemotherapeutic drugs. Nowadays, mesenchymal stem cells (MSCs) have been drawing great attention as cellular vehicles for gene delivery systems. Inherent characteristics of MSCs make them particularly attractive gene therapy tools in cell therapy. They have been used largely for their remarkable homing property toward tumor sites and availability from many different adult tissues and show anti-inflammatory actions in some cases. They do not stimulate proliferative responses of lymphocytes, suggests that MSCs have low immunogenicity and could avoid immune rejection. This review summarizes the current state of knowledge about genetically modified MSCs that enable to co-transduce a variety of therapeutic agents including suicide genes (i.e., cytosine deaminase, thymidine kinase) in order to exert potent anti-carcinogenesis against various tumors growth. Moreover, we highlighted the role of exosomes released from MSCs as new therapeutic platform for targeting various therapeutic agents.

Treatment of advanced gastrointestinal cancer with genetically modified autologous mesenchymal stem cells: Results from the phase 1/2 TREAT‐ME‐1 trial

“…can easily be isolated and expanded in large amounts from adult mammals without major ethical concerns; (b.) undergo targeted tropism towards growing tumors; (c.) migrate deep into the tumor microenvironment; (d.) differentiate into cells of the tumor stroma (cancer‐associated fibroblasts, pericytes and endothelial cells); (e.) have low immunogenicity and can potentially avoid immune rejection …”

The Dynamic Roles of Mesenchymal Stem Cells in Colon Cancer

“…In vivo studies have repeatedly shown that MSCs are trapped after intravenous injection [ 82 , 83 ]. Many existing methods are used to modify MSCs and the most commonly used are genetically modified MSCs [ 84 , 85 ]. The cells can transport the agents into the tumor microenvironment and greatly reduce the immune reaction in vivo through high concentration anticancer agents target tumor site.…”

Genetically‑modified stem cells in treatment of human diseases: Tissue kallikrein (KLK1)‑based targeted therapy (Review)

“…Viral vectors are particularly appealing because they can enable high transduction efficiency and, depending on the type of virus used, can deliver long-term stable transgene expression. The safety of cell-based therapy with the use of viral vectors is a crucial issue that has not been resolved yet, but advances in vector design have helped towards this direction ( 23 , 95 ). For example, MSCs genetically modified to express VEGF have been shown to enhance the cardioprotective effects of MSCs followed by angiogenesis effects for the treatment of acute MI, whereas Akt gene- or heme oxygenase-1 ( HO-1 ) gene-modified MSCs have been shown to dramatically improve ischemic cardiac function and MSC viability and prevent ventricular remodeling and apoptosis of cardiomyocytes and endothelial cells, thus restoring the function of infarcted hearts ( 91 , 96 – 98 ).…”