Bioengineered Mesenchymal Stem/Stromal Cells in Anti-Cancer Therapy: Current Trends and Future Prospects

Abstract

Mesenchymal stem/stromal cells (MSCs) are one of the most widely used cell types in advanced therapies due to their therapeutic potential in the regulation of tissue repair and homeostasis, and immune modulation. However, their use in cancer therapy is controversial: they can inhibit cancer cell proliferation, but also potentially promote tumour growth by supporting angiogenesis, modulation of the immune milieu and increasing cancer stem cell invasiveness. This opposite behaviour highlights the need for careful and nuanced use of MSCs in cancer treatment. To optimize their anti-cancer effects, diverse strategies have bioengineered MSCs to enhance their tumour targeting and therapeutic properties or to deliver anti-cancer drugs. In this review, we highlight the advanced uses of MSCs in cancer therapy, particularly as carriers of targeted treatments due to their natural tumour-homing capabilities. We also discuss the potential of MSC-derived extracellular vesicles to improve the efficiency of drug or molecule delivery to cancer cells. Ongoing clinical trials are evaluating the therapeutic potential of these cells and setting the stage for future advances in MSC-based cancer treatment. It is critical to identify the broad and potent applications of bioengineered MSCs in solid tumour targeting and anti-cancer agent delivery to position them as effective therapeutics in the evolving field of cancer therapy.

Keywords: anti-cancer therapy; cell therapy; mesenchymal stem/stromal cells; targeted therapy; therapeutic vehicles.

Figure 1

Dual roles of MSCs in tumour dynamics. MSCs possess unique properties that make them promising therapeutic agents. However, these same properties can also influence tumour development. MSCs can release a variety of factors that have both pro- and anti-tumour effects, influencing cellular tumour processes such as survival, proliferation, angiogenesis and chemotherapy resistance. These paracrine factors can be released directly into the tumour microenvironment or transported via extracellular vesicles (EVs). Created using BioRender.

Figure 2

Different strategies to enhance the anti-tumour properties of both MSCs and MSC-derived EVs. (1) MSCs can be used to deliver chemotherapeutic drugs or bioactive molecules (e.g., interferons, interleukins, chemokines, and pro-apoptotic, anti-tumour or anti-angiogenic molecules) directly into the tumour microenvironment. (2) MSCs are effective oncolytic virus carriers because they can be easily infected, allowing viral replication and sustained viability until they reach the tumour microenvironment. (3) MSCs can be genetically engineered to carry suicide genes that encode specific enzymes that convert non-toxic prodrugs into cytotoxic metabolites directly in the tumour cells, increasing the specificity and efficacy of therapy while reducing systemic toxicity. (4) Bioengineered MSC-derived EVs can be customized to improve their therapeutic efficacy and capacity to deliver specific anti-cancer agents. (5) Various bioengineering strategies are being investigated to improve MSC homing to tumours, including priming with bioactive molecules, genetic engineering, enzymatic modification and ligand conjugation techniques. Created using BioRender.