The uncertain role of unmodified mesenchymal stem cells in tumor progression: what master switch?

Mesenchymal stem cells (MSCs) are emerging as promising gene vectors for cancer therapy because of their unique characteristics, including the ease of their expansion and genetic modification and their remarkable tumor-tropic properties. However, there remains a concern that MSCs may promote cancer progression. Surprisingly, there are conflicting reports within the literature describing both the promotion and inhibition of cancer progression by MSCs. The reasons for this discrepancy are still unknown. The surface markers, differentiation ability, and tumorigenic roles of MSCs, as well as their effect on immunoregulation, produce heterogeneity. In this review, we describe the heterogeneity of MSCs by the species from which they are derived, the methodology for their isolation and the context of their interactions with cancer cells. The conflicting roles of MSCs in tumor progression may be attributable to the bimodal effect of unmodified MSCs on immunoregulation. MSCs have been reported to suppress T-cell function and inhibit graft-versus-host disease (GVHD). On the other hand, MSCs elicit the graft-versus-tumor (GVT) effect in some cases. Selective allodepletion may be used to dissociate GVHD from the GVT effect. Understanding the conditions that balance GVHD and the GVT effect of MSCs may be crucial to advance cancer therapy research with respect to MSCs.