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

Abstract

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.

Tumor‐associated mesenchymal stem cells inhibit naïve T cell expansion by blocking cysteine export from dendritic cells

“…MSCs have been most commonly applied clinically in adoptive cell therapy approaches based on their potent regenerative capacity . Despite some controversy on the role of MSCs in tumor setting, it is believed that these cells may support tumor progression by suppressing the host immune response . Inadequate evidence on T cell inhibition by tumor conditioned MSCs prompted us to explore the role of TC‐MSCs on DC/T cell function(s) in vitro .…”

“…38 Despite some controversy on the role of MSCs in tumor setting, 38 it is believed that these cells may support tumor progression by suppressing the host immune response. 39,40 Inadequate evidence on T cell inhibition by tumor conditioned MSCs prompted us to explore the role of TC-MSCs on DC/T cell function(s) in vitro. We report the following novel observations: first, TC-MSCs suppress proliferation and late phase effector functions (IFNg secretion and tumor cell cytotoxicity) of T cells without affecting their early activation; second, TC-MSC mediated suppression of T cell proliferation is contact independent and mediated by TC-MSC-produced IL-10; third, this IL-10 represses cystathionase gene expression in DCs and thereby inhibits DC export of cysteine required by cognate T cells for their optimal proliferation; and finally, pSTAT3 may directly bind with a GAS motif present within the cystathionase promoter of DC after IL-10 stimulation, leading to repression of cystathionase transcription.…”

Immunomodulatory effects of umbilical cord‐derived mesenchymal stem cells

“…However, Liyang et al . reported that CD133‐positive MSCs can be isolated from UCB . They had high proliferative potential and were passaged every 5–6 days.…”

Detection of endogenously circulating mesenchymal stem cells in human cancer patients

“…MSCs can affect many cancer hallmarks such as angiogenesis, metastasis, antiapoptosis, and evasion of the immune system. 2,13,21,22,34,35 The presence, route, and effects of endogenously circulating MSCs, however, have not been intensively studied. According to some, they are difficult (if not impossible) to detect.…”