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.
Highlights
Due to their tropism to the tumor niche, mesenchymal stem cells (MSCs) are promising vectors for the delivery of antitumor agents
That following accumulation at the sites of tumor formation and growth, Mesenchymal stem cells (MSCs) differentiate into pericytes or tumor-associated fibroblasts (TAF) thereby forming a growth supporting microenvironment and secreting such trophic factors as vascular endothelial growth factor (VEGF), interleukin 8 (IL-8), transforming growth factor β (TGF-β), epidermal growth factor (EGF), and platelet-derived growth factor (PDGF). (Nwabo Kamdje et al, 2017)
Due to tropism to the tumor microenvironment, MSCs can be considered as promising vectors for the delivery of antitumor agents (Figure 1)
Summary
Due to their tropism to the tumor niche, mesenchymal stem cells (MSCs) are promising vectors for the delivery of antitumor agents. MSCs can migrate to sites of trauma and injury following the gradient of chemo-attractants in the extracellular matrix (ECM) and peripheral blood (Son et al, 2006) and local factors, such as hypoxia, cytokine environment and Toll-like receptors ligands, where upon arrival these local factors promote MSCs to express growth factors that accelerate tissue regeneration (Rustad and Gurtner, 2012) It is believed, that following accumulation at the sites of tumor formation and growth, MSCs differentiate into pericytes or tumor-associated fibroblasts (TAF) thereby forming a growth supporting microenvironment and secreting such trophic factors as vascular endothelial growth factor (VEGF), interleukin 8 (IL-8), transforming growth factor β (TGF-β), epidermal growth factor (EGF), and platelet-derived growth factor (PDGF). There is a consensus that MSCs have enhanced tropism toward tumors which make them ideal vector candidates for targeted anti-tumor therapy
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