Mesenchymal stem cells loaded with paclitaxel inhibit tumor growth and angiogenesis

Background: Mesenchymal stem cells (MSCs) may represent an ideal candidate to deliver anti-cancer drugs. In a previous study, we demonstrated that simple exposure of bone marrow (BM) derived MSCs to high doses of Doxorubicin, led them to acquire anti-proliferative potential towards co-cultured haematopoitic stem cells (HSCs). We thus hypothesized whether MSCs, once primed in vitro with anti-cancer drugs and then localized near cancer cells, can inhibit proliferation. Methods: Paclitaxel (PTX) was used to prime culture of mouse and human MSCs. Incorporation of PTX into MSCs (MSCsPTX) was studied by using FITC-labelled-PTX and analyzed by FACS and confocal microscopy. Release of PTX in culture medium by MSCsPTX was investigated by HPLC. Culture of Endothelial cells (ECs) and aorta ring assay were used to test the anti-angiogenic activity of MSCsPTX, while anti-tumor activity was tested in vitro on the proliferation of different tumor cell lines and in vivo by co-transplanting MSCsPTX with cancer cells in mice. Results: MSCs were able to rapidly incorporate PTX and could slowly release PTX in the culture medium in a time dependent manner. Primed MSCsPTX acquired a potent anti-tumor and anti-angiogenic activity in vitro that was dose dependent, and demonstrable by using their conditioned medium or by co-culture assay. Finally, MSCsPTX co-injected in immunodeficient mice with DU145 and B16 cancer cells, significantly delayed tumor takes and reduced tumor growth. Conclusions: These data demonstrate that, without any genetic manipulation, MSCs can uptake and subsequently slowly release PTX, becoming a potential new tool for cancer therapy.