www.CRTER.orgXuQiao-yan,Attendingphysician,DepartmentofRespiratoryMedicine,thePeople’sHospitalofLaizhou,Yantai261400,ShandongProvince,Chinaqiaoyanx@yahoo.cnCorrespondingauthor:WangJi-chang,M.D.,Attendingphysician,DepartmentofPlasticSurgery,theSecondHospitalofShandongUniversity,Jinan250033,ShandongProvince,Chinawangjichangxu@163.comAccepted:2013-09-18(201303132/WJ)中国组织工程研究第17卷第49期2013–12–03出版ChineseJournalofTissueEngineeringResearchDecember3,2013Vol.17,No.49doi:10.3969/j.issn.2095-4344.2013.49.003[http://www.crter.org]XuQY,XiaL,WangJC.Hypoxicpreconditioningeffectsontheabilityofbonemarrowmesenchymalstemcellstoleranttoischemiaandhypoxia.ZhongguoZuzhiGongchengYanjiu.2013;17(49):8474-8480.Hypoxicpreconditioningeffectsontheabilityofbonemarrowmesenchymalstemcellstoleranttoischemiaandhypoxia*XuQiao-yan1,XiaLin2,WangJi-chang31DepartmentofRespiratoryMedicine,thePeople’sHospitalofLaizhou,Yantai261400,ShandongProvince,China2DepartmentofPlasticSurgery,QiluHospitalofShandongUniversity,Jinan250012,ShandongProvince,China3DepartmentofPlasticSurgery,theSecondHospitalofShandongUniversity,Jinan250033,ShandongProvince,ChinaAbstractBACKGROUND:Accordingtothepreviousstudies,itisknownthatbonemarrowmesenchymalstemcellsliveinthephysiologicalenvironmentofloweroxygenconcentrationcomparedwiththecommoncultureconcentration(20%-21%).Hypoxiacanpromotebonemarrowmesenchymalstemcellsproliferationandmaintainthecharacteristicsofdifferentiationpotential.OBJECTIVE:Tounderstandthebiologicalcharacteristicsofbonemarrowmesenchymalstemcellsafterhypoxicpreconditioning,andsearchforinvitrobasisforbonemarrowmesenchymalstemcellstherapyinvivowithhypoxicpreconditioningstrategy.METHODS:Afterpassageandinoculation,bonemarrowmesenchymalstemcellswereculturedinthehypoxicincubator(1%O2,5%CO2).Bonemarrowmesenchymalstemcellsculturedinthenormoxicincubator(20%O2,5%CO2)servedascontrols.RESULTSANDCONCLUSION:Comparedwithbonemarrowmesenchymalstemcellsculturedundernormoxia(20%O2),bonemarrowmesenchymalstemcellsculturedunderhypoxia(1%O2)begantodisplayexponentialgrowthphaseafteralongerincubationperiod.Hypoxia(1%O2)wasnotthelethalconditionforbonemarrowmesenchymalstemcells.Cellsurvivalratesofbothgroupsreducedovertime,whilethoseofbonemarrowmesenchymalstemcellsculturedundernormoxiareducedfaster(P<0.05).Surfacemarkersexpressionofbonemarrowmesenchymalstemcells,includingCD29(+),CD90(+),CD31(-),CD45(-),afterhypoxicpreconditioningdidnotchangegreatlywhencomparedwiththeresultsbeforehypoxicpreconditioning.Thehypoxiapreconditionedbonemarrowmesenchymalstemcellsdidnotdifferentiateintovascularendothelialcells.Hypoxia-induciblefactor-1αproteinexpressionwaspromotedafter24hoursto48hourshypoxicpreconditioning,andtherewassignificantdifferencebetweenthetwotimepoints(P<0.05).Vascularendothelialgrowthfactorexpressionincreasedatbothtranscriptionalandproteinlevelsafter48hourshypoxicpreconditioning(P<0.05).Cultureunderhypoxia(1%O2)doesnotproducealethaleffectonbonemarrowmesenchymalstemcellsandcanbeusedforhypoxicpreconditioning.Surfacemarkersofbonemarrowmesenchymalstemcellsafter48hourshypoxicpreconditioningexhibitnogreatchangesandthehypoxiapreconditionedbonemarrowmesenchymalstemcellsmaintainthecharacteristicsofstemness.Hypoxicpreconditioningcanpromotetheabilityofbonemarrowmesenchymalstemcellstosurviveunderhypoxia/ischemiccondition.Theactivationoftheh...