AgeingResearchReviews10(2011)93–103ContentslistsavailableatScienceDirectAgeingResearchReviewsjournalhomepage:www.elsevier.com/locate/arrReviewMSCs:Biologicalcharacteristics,clinicalapplicationsandtheiroutstandingconcernsYi-LingSi,Ya-LiZhao,Hao-JieHao,Xiao-BingFu∗,Wei-DongHan∗InstituteofBasicMedicineScience,ChinesePLAGeneralHospital,28FuxingRoad,Beijing100853,ChinaarticleinfoArticlehistory:Received29June2010Receivedinrevisedform29July2010Accepted4August2010Keywords:MesenchymalstemcellsBiologicalcharacteristicsTissueregenerationDiseasetherapyClinicaltrialsOutstandingquestionsabstractMesenchymalstemcells(MSCs)aremulti-potentadultstemcellsharboringmulti-lineagedifferenti-ationpotentialandimmunosuppressivepropertiesthatmakeMSCsanidealcandidatecelltypeforimmunomodulationandregenerativemedicine.Currently,MSC-relatedresearchesandclinicaltrialshaveevokedexcitingpromiseinavarietyofdisordersandtissueregeneration.However,itmustberecognizedthatseveralcriticalpotentialproblemshavealsoemergedfromcurrentclinicaltrials,forexample:(1)theindefiniteassociationbetweenthephenotypiccharacteristicsandthebiologicalfunc-tionsofMSCs;(2)thelackofclinicaldatatosupportthelong-termsafetyofMSCs;(3)theneedforfurtherclarificationofmultiplemechanismsofMSCtransplantactionsinvivo;and(4)thelackofcomparabilityofMSCtransplantefficacy.Therefore,MSC-basedtherapiescouldnotyetbeconsideredaroutinetreatmentintheclinic.Basedonthese,weproposedthatlarge-scaleandmulti-centerclinicaltrialsofMSC-basedtherapiesshouldbeinitiatedunderstrictsupervision.TheseinterventionsmighthelptoestablishanewclinicalparadigmtoturnMSCtransplantationintoaroutinetherapyforatleastsomediseasesinthenearfuture.©2010ElsevierB.V.Allrightsreserved.1.IntroductionMesenchymalstemcells(MSCs)areaheterogeneoussubsetofstromalstemcellsthathavetheabilityofself-renewalandmul-tipotency,whichcoulddifferentiateintocellsofthemesodermallineagesandotherembryoniclineages,includingadipocytes,osteo-cytes,chondrocytes,hepatocytes,neurons,musclecells,epitheli...