Mesenchymal Stem Cell as a Vector for Gene and Cell therapy Strategies

Mesenchymal Stromal/Stem Cells: A New Era in the Cell-Based Targeted Gene Therapy of Cancer

“…The non-specific targeting by administering the non-viral/viral vectors and their systemic distribution throughout the circulation can result in undesired adverse effects. Since the discovery of ability of transgene mesenchymal stromal/stem cells (MSCs) to selectively migrate toward the injured and tumor site(s), the gene therapy of cancers experienced a substantial leap ahead ( 3 , 4 ). But despite the remarkable progress in the field of cancer gene therapy, there are two main obstacles still remaining, including the difficulty in obtaining a suitable drug carrier or transgene vehicle that can selectively migrate toward tumor location and the difficulty in discovering an eligible vehicle that can resist within the biased and hostile microenvironment of the tumor ( 5 , 6 ).…”

“…The results hold out tremendous promise for MSCs due to their inherent tropism to tumor sites and immunomodulatory properties. MSCs are non-hematopoietic stem cells originally found within bone marrow but also present in other tissues, including adipose tissue, dental pulp, muscles, and skin ( 3 , 4 ). Dental-tissue is an easily accessible source of stem cells.…”

“…They can be differentiated into various types of cells, including adipose tissue, bone tissue, and cartilage tissue. Although MSCs constitute a small population of bone marrow cells, they also play an apparent role in hematopoiesis ( 3 , 8 ). In other words, using MSCs opens novel opportunities for a wide spectrum of clinical applications, such as the cell therapy, regenerative medicine, cancer gene therapy and treatment of graft versus host disease (Tables 1 and 2 ) due to their remarkable capacity for proliferation and differentiation, immunoregulatory effects, tendency toward the injured tissues and ease of isolation and expansion in vitro ( 3 ).…”

“…Although MSCs constitute a small population of bone marrow cells, they also play an apparent role in hematopoiesis ( 3 , 8 ). In other words, using MSCs opens novel opportunities for a wide spectrum of clinical applications, such as the cell therapy, regenerative medicine, cancer gene therapy and treatment of graft versus host disease (Tables 1 and 2 ) due to their remarkable capacity for proliferation and differentiation, immunoregulatory effects, tendency toward the injured tissues and ease of isolation and expansion in vitro ( 3 ). In addition, low expression of costimulatory molecules by MSCs makes them nearly unidentifiable by immune system and as a consequence non-immunogen, empowering them for the stealthy movement and migration through the circulation.…”

“…(4) Immuno-gene therapy: increasing the immunogenicity of the tumor cells/tissue to stimulate immune cell response against tumor ( 1 ) (Figure 1 ). The major hallmark explained for MSCs as the cell carriers is the ease of introducing new therapeutic genes into their genetic material and subsequently the simplicity of utilizing them for in vivo trials ( 3 , 12 ). Recent studies have shown the successful application of lentivirus, retrovirus, or plasmid as the operational vectors to transfer genes into MSCs ( 13 , 14 ) (Table 3 ).…”