In vitro and in vivo interactions between glioma and marrow-isolated adult multilineage inducible (MIAMI) cells.

The prognosis of patients with malignant glioma remains extremely poor despite surgery and improvements in radio- and chemo-therapies. We recently showed that marrow-isolated adult mutilineage inducible (MIAMI) cells, a subpopulation of human mesenchymal stromal cells (MSCs), can serve as cellular carriers of drug-loaded nanoparticles to brain tumors. However, the safety of MIAMI cells as cellular treatment vectors in glioma therapy must be evaluated, in particular their effect on glioma growth and their fate in a tumor environment. In this study, we showed that MIAMI cells were able to specifically migrate toward the orthotopic U87MG tumor model and did not influence its growth. In this model, MIAMI cells did not give rise to cells resembling endothelial cells, pericytes, cancer-associated fibroblasts (CAFs), or astrocytes. Despite these encouraging results, the effects of MIAMI cells may be glioma-dependent. MIAMI cells did not migrate toward the orthotopic Lab1 GB and they can induce the proliferation of other glioma cell lines in vitro. Furthermore, a fraction of MIAMI cells was found to be in a state of proliferation in the U87MG tumor environment. These findings indicate that the use of MIAMI cells as cellular treatment vectors for malignant tumors must be controlled. These cells may be used as "suicide vectors": vectors for killing not only tumor cells but themselves.