Premium
Mesenchymal stromal cells primed with P aclitaxel attract and kill leukaemia cells, inhibit angiogenesis and improve survival of leukaemia‐bearing mice
Author(s) -
Pessina Augusto,
Coccè Valentina,
Pascucci Luisa,
Bonomi Arianna,
Cavicchini Loredana,
Sisto Francesca,
Ferrari Maura,
Ciusani Emilio,
Crovace Antonio,
Falchetti Maria Laura,
Zicari Sonia,
Caruso Arnaldo,
Navone Stefania,
Marfia Giovanni,
Benetti Anna,
Ceccarelli Piero,
Parati Eugenio,
Alessandri Giulio
Publication year - 2013
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1111/bjh.12196
Subject(s) - mesenchymal stem cell , angiogenesis , stromal cell , paclitaxel , priming (agriculture) , cancer research , in vitro , in vivo , apoptosis , immunology , biology , chemotherapy , pharmacology , medicine , microbiology and biotechnology , biochemistry , botany , germination
Summary Current leukaemia therapy focuses on increasing chemotherapy efficacy. Mesenchymal stromal cells ( MSC s) have been proposed for carrying and delivery drugs to improve killing of cancer cells. We have shown that MSC s loaded with Paclitaxel ( PTX ) acquire a potent anti‐tumour activity. We investigated the effect of human MSC s ( hMSC s) and mouse SR 4987 loaded with PTX ( hMSCsPTX and SR 4987 PTX ) on MOLT ‐4 and L 1210, two leukaemia cell ( LCs ) lines of human and mouse origin, respectively. SR 4987 PTX 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 BDF 1‐mice‐bearing L 1210, the intraperitoneal administration of SR 4987 PTX doubled mouse survival time. In vitro, both hMSC s and hMSCsPTX released chemotactic factors, bound and formed rosettes with LC s. In ultrastructural analysis of rosettes, hMSCsPTX showed no morphological alterations while the attached LC s were apoptotic and necrotic. hMSC s and hMSCsPTX released molecules that reduced LC adhesion to microvascular endothelium ( hMEC s) and down‐modulated ICAM 1 and VCAM 1 on hMEC s. Priming hMSC s 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.