title: Mesenchymal stromal cells primed with Paclitaxel attract and kill leukaemia cells, inhibit angiogenesis and improve survival of leukaemia-bearing mice.
abstract: Current leukaemia therapy focuses on increasing chemotherapy efficacy. Mesenchymal stromal cells (MSCs) have been proposed for carrying and delivery drugs to improve killing of cancer cells. We have shown that MSCs loaded with Paclitaxel (PTX) acquire a potent anti-tumour activity. We investigated the effect of human MSCs (hMSCs) and mouse SR4987 loaded with PTX (hMSCsPTX and SR4987PTX) on MOLT-4 and L1210, two leukaemia cell (LCs) lines of human and mouse origin, respectively. SR4987PTX and hMSCsPTX showed strong anti-LC activity. hMSCsPTX, co-injected with MOLT-4 cells or intra-tumour injected into established subcutaneous MOLT-4 nodules, strongly inhibited growth and angiogenesis. In BDF1-mice-bearing L1210, the intraperitoneal administration of SR4987PTX doubled mouse survival time. In vitro, both hMSCs and hMSCsPTX released chemotactic factors, bound and formed rosettes with LCs. In ultrastructural analysis of rosettes, hMSCsPTX showed no morphological alterations while the attached LCs were apoptotic and necrotic. hMSCs and hMSCsPTX released molecules that reduced LC adhesion to microvascular endothelium (hMECs) and down-modulated ICAM1 and VCAM1 on hMECs. Priming hMSCs with PTX is a simple procedure that does not require any genetic cell manipulation. Once the effectiveness of hMSCsPTX on established cancers in mice is proven, this procedure could be proposed for leukaemia therapy in humans.
authors.affiliation: Department of Biomedical, Surgical and Dental Sciences, University of Milan, Milan, Italy. augusto.pessina@unimi.it
authors.forename: Augusto
authors.initials: A
authors.lastname: Pessina
authors.forename: Valentina
authors.initials: V
authors.lastname: Coccè
authors.forename: Luisa
authors.initials: L
authors.lastname: Pascucci
authors.forename: Arianna
authors.initials: A
authors.lastname: Bonomi
authors.forename: Loredana
authors.initials: L
authors.lastname: Cavicchini
authors.forename: Francesca
authors.initials: F
authors.lastname: Sisto
authors.forename: Maura
authors.initials: M
authors.lastname: Ferrari
authors.forename: Emilio
authors.initials: E
authors.lastname: Ciusani
authors.forename: Antonio
authors.initials: A
authors.lastname: Crovace
authors.forename: Maria Laura
authors.initials: ML
authors.lastname: Falchetti
authors.forename: Sonia
authors.initials: S
authors.lastname: Zicari
authors.forename: Arnaldo
authors.initials: A
authors.lastname: Caruso
authors.forename: Stefania
authors.initials: S
authors.lastname: Navone
authors.forename: Giovanni
authors.initials: G
authors.lastname: Marfia
authors.forename: Anna
authors.initials: A
authors.lastname: Benetti
authors.forename: Piero
authors.initials: P
authors.lastname: Ceccarelli
authors.forename: Eugenio
authors.initials: E
authors.lastname: Parati
authors.forename: Giulio
authors.initials: G
authors.lastname: Alessandri
mesh_terms: D000818:Animals; D002450:Cell Communication / Q000502:physiology*; D048708:Cell Growth Processes / Q000502:physiology; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D006801:Humans; D007938:Leukemia / Q000188:drug therapy / Q000473:pathology* / Q000601:surgery / Q000628:therapy*; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods*; D059630:Mesenchymal Stem Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D008819:Mice, Nude; D009389:Neovascularization, Pathologic / Q000188:drug therapy / Q000473:pathology; D017239:Paclitaxel / Q000494:pharmacology*; D023041:Xenograft Model Antitumor Assays
chemical_list: D017239:Paclitaxel