An overview of mesenchymal stem cells and their potential therapeutic benefits in cancer therapy

Abstract

There has been increased interest in using stem cells for regenerative medicine and cancer therapy in the past decade. Mesenchymal stem cells (MSCs) are among the most studied stem cells due to their unique characteristics, such as self-renewal and developmental potency to differentiate into numerous cell types. MSC use has fewer ethical challenges compared with other types of stem cells. Although a number of studies have reported the beneficial effects of MSC-based therapies in treating various diseases, their contribution to cancer therapy remains controversial. The behaviour of MSCs is determined by the interaction between intrinsic transcriptional genes and extrinsic environmental factors. Numerous studies continue to emerge, as there is no denying the potential of MSCs to treat a wide variety of human afflictions. Therefore, the present review article provided an overview of MSCs and their differences compared with embryonic stem cells, and described the molecular mechanisms involved in maintaining their stemness. In addition, the article examined the therapeutic application of stem cells in the field of cancer. The present article also discussed the current divergent roles of MSCs in cancer therapy and the future potential in this field.

Keywords: cancer therapy; cell-based therapies; mesenchymal stem cells; therapeutic stem cells.

Figure 1.

Summary of the mechanism of action of MSCs on the modulation of tumour cell growth. (A) MSCs regulate the immunomodulatory process by secreting several soluble factors that interfere with the immune system. MSCs also reveal their immunomodulatory potential through cell-cell interaction by activating monocytes, eosinophils, basophils and neutrophils. (B) MSCs are multipotent progenitors able to migrate, home and differentiate into CAFs. (C) MSCs have the ability to form a cancer stem cell niche in vivo where tumour cells can preserve the potential to proliferate and sustain the malignant process. (D) Paracrine effects of the secretome contributes to the duality function of MSCs. For example, they decrease levels in Stat3 and IGF-1R, and increase levels of IL-4 and IL-10 to inhibit tumour growth, while also increasing levels of IL-6 and VEGF to promote tumour growth. https://biorender.com/ created the figure. MSCs, mesenchymal stem cells; CAF, cancer-associated fibroblasts; Stat3, signal transducer and activator of transcription 3; IGF-1R, insulin-like growth factor 1 receptor; IL-4, interleukin-4; IL-10, interleukin-10; IL-6, interleukin-6; VEGF, vascular endothelial growth factor; PDGF, platelet-derived growth factor; GM-CSF, granulocyte/macrophage colony stimulating factor.

Figure 2.

Potential therapeutic strategies of MSCs in cancer therapy. (A) Priming TLR-4-primed MSCs (MSC1) and TLR-3-primed MSCs (MSC2) for the immunomodulatory phenotype. (B) Vector delivers the oncolytic virus to the tumour site for growth inhibition. (C) Genetic engineering using viral vectors to introduce plasmid RNA and DNA. (D) Priming MSCs with anticancer drugs to improve their pharmacological properties. https://biorender.com/ created the figure. MSCs, mesenchymal stem cells; TLR, Toll-like receptor.