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Review
. 2017 Dec 18:8:1770.
doi: 10.3389/fimmu.2017.01770. eCollection 2017.

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

Faroogh Marofi  1 , Ghasem Vahedi  2 , Alireza Biglari  3 , Abdolreza Esmaeilzadeh  4   5 , Seyyed Shamsadin Athari  4
Affiliations
Review

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

Faroogh Marofi et al. Front Immunol. .

Abstract

In recent years, in light of the promising potentials of mesenchymal stromal/stem cells (MSCs) for carrying therapeutic anticancer genes, a complete revisitation on old chemotherapy-based paradigms has been established. This review attempted to bring forward and introduce the novel therapeutic opportunities of using genetically engineered MSCs. The simplicities and advantages of MSCs for medical applications make them a unique and promising option in the case of cancer therapy. Some of the superiorities of using MSCs as therapeutic gene micro-carriers are the easy cell-extraction procedures and their abundant proliferation capacity in vitro without losing their main biological properties. Targeted therapy by using MSCs as the delivery vehicles of therapeutic genes is a new approach in the treatment of various types of cancers. Some of the distinct properties of MSCs, such as tumor-tropism, non-immunogenicity, stimulatory effect on the anti-inflammatory molecules, inhibitory effect on inflammatory responses, non-toxicity against the normal tissues, and easy processes for the clinical use, have formed the basis of attention to MSCs. They can be easily used for the treatment of damaged or injured tissues, regenerative medicine, and immune disorders. This review focused on the drugability of MSCs and their potential for the delivery of candidate anticancer genes. It also briefly reviewed the vectors and methods used for MSC-mediated gene therapy of malignancies. Also, the challenges, limitations, and considerations in using MSCs for gene therapy of cancer and the new methods developed for resolution of these problems are reviewed.

Keywords: cancer; cell therapy; gene therapy; mesenchymal stem cells; vector.

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Figures

Figure 1
Figure 1
The schematic picture represents the strategies of anticancer gene therapy using mesenchymal stromal/stem cells (MSCs) as gene vehicles. Anticancer gene can be transferred into MSCs by three main groups of techniques; viral vectors, non-viral vectors, and physical methods. There are two approaches for gene therapy of cancer patients; ex vivo, in vivo. Four groups of anticancer gene therapies have been developed to date; augmentation-, silencing-, suicide-, and immune-gene therapy.
Figure 2
Figure 2
The schematic picture shows the mechanism of mesenchymal stromal/stem cells (MSCs) migration/homing toward injured/cancer tissues. MSCs moving toward target tissue can be characterized by three stages: flowing through blood-flow, moving toward chemoattractants, and adhesion by surface receptors, translocation from blood flow toward injured/cancer tissue. The figure also demonstrates the endothelial–MSCs interactions, receptors, and the chemokines which are involved in MSCs migration procedures. The tumor-affected endothelial cells produce selectins, integrin ligands, and chemokines. These secretory stimulants and chemoattractants recruited MCSs to the tumor site.
Figure 3
Figure 3
A schematic picture depicts the procedures for the isolation, culture, gene transfer, and in vivo administration of the mesenchymal stromal/stem cells (MSCs). The schema also shows the routes that the MSCs traverse toward their target; tumor sites, and cancerous cells. The abbreviations on the figure include the following: BM, bone marrow; UCB, umbilical cord blood; AT, adipose tissue; IV, intravenous; IT, Intrathecal; IP, Intraperitoneal.
See this image and copyright information in PMC

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