Mesenchymal stromal cells primed with Paclitaxel attract and kill leukaemia cells, inhibit angiogenesis and improve survival of leukaemia‐bearing mice

Abstract

Current treatment of leukemia focuses on increasing chemotherapy efficacy. Mesenchymal stromal cells (MSCs) have been proposed for carrying and delivery drugs to improve cancer cells-specific killing. Recently, we have shown that MSCs loaded with the anti-cancer drug Paclitaxel (PTX), acquire a potent anti-tumor activity. To expand these findings, we here investigate the effect of human MSCs (hMSCs) and mouse SR4987 loaded with PTX (hMSCsPTX and SR4987PTX) on Molt-4 and L1210, two Leukemia cell (LC) lines of human and mouse origin respectively. We found that SR4987PTX and hMSCsPTX had a strong anti-LC activity. HMSCsPTX co-injected with Molt-4 or intra-tumor injected into an established subcute Molt-4 nodules strongly inhibited growth and angiogenesis. In syngenic BDF1 mice-bearing L1210, the intraperitoneal administration of SR4987PTX doubled mice survival time. In vitro, both hMSCs and hMSCsPTX released chemotactic factors, bound and formed rosette with LCs. By ultrastructural analysis of rosette, hMSCsPTX showed no morphological alterations while the attached LCs were apoptotic and necrotic. Finally, MSCs and MSCsPTX released molecules that reduced LCs adhesion to microvascular endothelium (hMECs) and down-modulated the adhesion molecules ICAM-1 and VCAM-1 on hMECs. We conclude that, besides conventional chemotherapy, MSCsPTX could be a new therapeutic approach to treat Leukemia in humans