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Review
. 2018 Mar 20:9:259.
doi: 10.3389/fphar.2018.00259. eCollection 2018.

Application of Mesenchymal Stem Cells for Therapeutic Agent Delivery in Anti-tumor Treatment

Daria S Chulpanova  1 , Kristina V Kitaeva  1 , Leysan G Tazetdinova  1 , Victoria James  2 , Albert A Rizvanov  1 , Valeriya V Solovyeva  1
Affiliations
Review

Application of Mesenchymal Stem Cells for Therapeutic Agent Delivery in Anti-tumor Treatment

Daria S Chulpanova et al. Front Pharmacol. .

Abstract

Mesenchymal stem cells (MSCs) are non-hematopoietic progenitor cells, which can be isolated from different types of tissues including bone marrow, adipose tissue, tooth pulp, and placenta/umbilical cord blood. There isolation from adult tissues circumvents the ethical concerns of working with embryonic or fetal stem cells, whilst still providing cells capable of differentiating into various cell lineages, such as adipocytes, osteocytes and chondrocytes. An important feature of MSCs is the low immunogenicity due to the lack of co-stimulatory molecules expression, meaning there is no need for immunosuppression during allogenic transplantation. The tropism of MSCs to damaged tissues and tumor sites makes them a promising vector for therapeutic agent delivery to tumors and metastatic niches. MSCs can be genetically modified by virus vectors to encode tumor suppressor genes, immunomodulating cytokines and their combinations, other therapeutic approaches include MSCs priming/loading with chemotherapeutic drugs or nanoparticles. MSCs derived membrane microvesicles (MVs), which play an important role in intercellular communication, are also considered as a new therapeutic agent and drug delivery vector. Recruited by the tumor, MSCs can exhibit both pro- and anti-oncogenic properties. In this regard, for the development of new methods for cancer therapy using MSCs, a deeper understanding of the molecular and cellular interactions between MSCs and the tumor microenvironment is necessary. In this review, we discuss MSC and tumor interaction mechanisms and review the new therapeutic strategies using MSCs and MSCs derived MVs for cancer treatment.

Keywords: chemotherapy resistance; cytokines; membrane vesicles; mesenchymal stem cells; oncolytic viruses; suppressor genes; tumor microenvironment.

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Figures

FIGURE 1
FIGURE 1
Mesenchymal stem cells and tumor cells interaction as an MSC-based approach for cancer therapy. The chemotactic movement of MSCs toward a tumor niche is driven by soluble factors, such as VEGF, PDGF, IL-8, IL-6, bFGF or FGF2, SDF-1, G-CSF, GM-CSF, MCP1, HGF, TGF-β, and UPAR. Genetic modification of MSCs can be used to deliver a range of tumor-suppressing cargos directly into the tumor niche. These cargos include tumor suppressor (TRAIL, PTEN, HSV-TK/GCV, CD/5-FC, NK4, PEDF, apoptin, HNF4-α), oncolytic viruses, immune-modulating agents (IFN-α, IFN-γ, IL-2, IL-12, IL-21, IFN-β, CX3CL1), and regulators of gene expression (miRNAs and other non-coding RNAs). MSCs are also capable of delivering therapeutic drugs such as DOX, PTX, GCB, and CDDP within the tumor site. In addition to using MSCs directly, microvesicles (MVs) isolated from MSCs represent an alternative approach to delivering these agents.
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