BACKGROUNDMesenchymal stem cell(MSC)extracellular vesicles,particularly exosomes(Exos),are gaining recognition aspromising therapeutic tools for cancer due to their capacity to modulate tumor cell biology.Induced plur...BACKGROUNDMesenchymal stem cell(MSC)extracellular vesicles,particularly exosomes(Exos),are gaining recognition aspromising therapeutic tools for cancer due to their capacity to modulate tumor cell biology.Induced pluripotentstem cell-derived MSCs(iMSCs)revealed therapeutic characteristics compared with conventional MSCs due totheir proliferative capacity and enhanced differentiation potential.AIMTo study the impact of Exos derived from iMSCs(iMSC-Exos)and bone marrow MSCs(BMSC-Exos)on PANC1and MDA-MB-231 cancer cells.METHODSThe iMSCs and BMSCs were characterized based on the International Society for Cellular Therapy(2006)criteria byverifying the expression of MSC-specific markers and their differentiation potential.Exos were isolated from 48-hour conditioned media using sequential ultracentrifugation and characterized based on size,morphology,andexpression of surface markers including CD9,CD81,and CD63.PANC1 and MDA-MB-231 cells were treated withthe isolated Exos,and their effects on cell proliferation,apoptosis,senescence,and invasion were assessed.RESULTSIn PANC1 cells iMSC-Exos sustained antiproliferative activity for 48 hours(35%reduction,P<0.01)while BMSCExoshad a transient effect.In MDA-MB-231 cells,both Exos lowered proliferation significantly after 48 hours(~28%and~22%reduction,P<0.05).Notably,these antiproliferative effects were not associated with apoptosis,but an increase in senescence-like tumor cells was identified as the primary response with iMSC-Exos inducingapproximately 2.3-fold higher number of senescence-associatedβ-galactosidase-positive cells compared withBMSC-Exos across both cancer cell lines.Tumor cell invasion was markedly inhibited in PANC1 and MDA-MB-231cells in response to iMSC-Exos(~60%and~45%reduction,respectively,P<0.001),and only in PANC1 cells inresponse to BMSC-Exos.CONCLUSIONiMSC-Exos effectively inhibited tumor proliferation and invasion via a senescence-like mechanism.These resultsindicated that iMSC-Exos could serve as a cell-free cancer therapy and merit further animal model evaluation.展开更多
文摘BACKGROUNDMesenchymal stem cell(MSC)extracellular vesicles,particularly exosomes(Exos),are gaining recognition aspromising therapeutic tools for cancer due to their capacity to modulate tumor cell biology.Induced pluripotentstem cell-derived MSCs(iMSCs)revealed therapeutic characteristics compared with conventional MSCs due totheir proliferative capacity and enhanced differentiation potential.AIMTo study the impact of Exos derived from iMSCs(iMSC-Exos)and bone marrow MSCs(BMSC-Exos)on PANC1and MDA-MB-231 cancer cells.METHODSThe iMSCs and BMSCs were characterized based on the International Society for Cellular Therapy(2006)criteria byverifying the expression of MSC-specific markers and their differentiation potential.Exos were isolated from 48-hour conditioned media using sequential ultracentrifugation and characterized based on size,morphology,andexpression of surface markers including CD9,CD81,and CD63.PANC1 and MDA-MB-231 cells were treated withthe isolated Exos,and their effects on cell proliferation,apoptosis,senescence,and invasion were assessed.RESULTSIn PANC1 cells iMSC-Exos sustained antiproliferative activity for 48 hours(35%reduction,P<0.01)while BMSCExoshad a transient effect.In MDA-MB-231 cells,both Exos lowered proliferation significantly after 48 hours(~28%and~22%reduction,P<0.05).Notably,these antiproliferative effects were not associated with apoptosis,but an increase in senescence-like tumor cells was identified as the primary response with iMSC-Exos inducingapproximately 2.3-fold higher number of senescence-associatedβ-galactosidase-positive cells compared withBMSC-Exos across both cancer cell lines.Tumor cell invasion was markedly inhibited in PANC1 and MDA-MB-231cells in response to iMSC-Exos(~60%and~45%reduction,respectively,P<0.001),and only in PANC1 cells inresponse to BMSC-Exos.CONCLUSIONiMSC-Exos effectively inhibited tumor proliferation and invasion via a senescence-like mechanism.These resultsindicated that iMSC-Exos could serve as a cell-free cancer therapy and merit further animal model evaluation.
