TGF-β Mediates Homing of Bone Marrow-Derived Human Mesenchymal Stem Cells to Glioma Stem Cells

Although studies have suggested that bone marrow human mesenchymal stem cells (BM-hMSC) may be used as delivery vehicles for cancer therapy, it remains unclear whether BM-hMSCs are capable of targeting cancer stem cells, including glioma stem cells (GSC), which are the tumor-initiating cells responsible for treatment failures. Using standard glioma models, we identify TGF-beta as a tumor factor that attracts BM-hMSCs via TGF-beta receptors (TGF beta R) on BM-hMSCs. Using human and rat GSCs, we then show for the first time that intravascularly administered BM-hMSCs home to GSC-xenografts that express TGF-beta. In therapeutic studies, we show that BM-hMSCs carrying the oncolytic adenovirus Delta-24-RGD prolonged the survival of TGF-beta-secreting GSC xenografts and that the efficacy of this strategy can be abrogated by inhibition of TGFbR on BM-hMSCs. These findings reveal the TGF-beta/TGF beta R axis as a mediator of the tropism of BM-hMSCs for GSCs and suggest that TGF-beta predicts patients in whom BM-hMSC delivery will be effective. Cancer Res; 73(7); 2333-44. (C)2012 AACR.