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

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. Current data indicate that cancer incidence is steadily increasing in the World. There is high mortality statistic available in current decades. All of these highlighted the urgent need for more safer and more effective therapies. One of the principal challenges along cancer treatment is how to destroy malignant tumors without damaging healthy cells. A new approach that shows great promise in this area is employment of a suicide gene. In this way, we need an appropriate carrier for therapeutic gene delivery specific to cancer site. The application of anti-cancer gene-expressing MSCs for targeted cancer therapy is a novel and promising strategy. MSCs with important characteristic such as strong tumor tropism, unlimited packaging capacity and unique immunologic tolerance, could overcome current obstacles and successfully deliver these suicide genes. Although MSCs have anticancer capacity but based on some reports could have positive role in tumor progression. Eventually more researches required to find novel insights into MSCs biology, potential clinical application, and molecular mechanism for homing to tumor site.