Mesenchymal Stem Cells: How Can we Realize their Therapeutic Potential in Cancer Therapy?

Abstract

Mesenchymal stem cells home to the tumour stroma from the bone marrow, influencing early tumour development and metastasis. Mesenchymal stem cells have been shown to be promising vehicles for cancer therapy due to this tropism for tumour sites, their immunoprivileged status, easy extraction from bone marrow and facile transfection. Mesenchymal stem cells have been used to deliver gene therapy in the form of cytokines or adenovirus and as part of prodrug strategies. However, in order for these agents to be tested in clinical trials, the biology of mesenchymal stem cells must be further investigated. At present there is variation between research groups surrounding mesenchymal stem cell isolation and characterisation methods, as well as in how the cells are delivered to in vivo models, making studies hard to compare. Research examining the attraction of mesenchymal stem cells to tumours has found that the cells home towards a wide range of growth factors, cytokines and proteases. Once part of the tumour stroma, mesenchymal stem cells may have both pro-and anti-tumorigenic effects, increasing tumour growth, angiogenesis and metastasis and decreasing immune activation in some systems, and in others, reducing tumour cell proliferation and development of metastases. Understanding more precisely which subsets of mesenchymal stem cells support or undermine the development of the tumour at various timepoints will enable an effective clinical trial strategy for mesenchymal stem cell-based cancer therapies to be developed and replicated with different cancers and treatment sites.