Multipotentmesenchymalstemcells(MSCs),alsoknownasmesenchymalstromalcells,areaheterogeneousgroupofprogenitorcellsthathaveanimportantroleintissueregeneration.Theywerefirstdiscoveredinbonemarrowstromainthelate1960sandidentifiedas“colonyformingunitfibroblasts”(REF.1)buthavesincebeenfoundtoexistinalmostalltissues2.Theycanbeidentifiedbyapanelofsurfacemarkers(BOX1)andcaneasilybeisolatedfrommanytissues,suchasbonemarrow,adiposetissueandumbilicalcords2,3.MSCshavethecapacitytoselfrenewandtodifferentiateintoseveralcelltypes,includingadipocytes,osteoblastsandchondrocytes2–5.Assuch,thesecellsholdgreatpromiseforthetreatmentofvarioustissueinjuriesinbothpreclinicalandclinicalstudies—aneffectbelievedtobeexertedthroughthereplacementofdamagedcells.Interestingly,MSCsalsopossesstheabilitytomodulateimmuneresponses.Sincetheirfirstsuccessfulapplicationintreatinggraftversushostdisease(GvHD)in2004(REF.6),MSCshavebeenusedtoeffectivelytreatchronicinflammatorydiseasesandchronicwounds,suchassystemiclupuserythematosus,liverinjuryanddiabeticfoot7–10.Over700MSCbasedclinicaltrialsarecurrentlylistedontheclinicaltrialregistryoftheUSNationalInstitutesofHealth.Theseclinicaltrialsaremostlyfocusedoninflammatorydiseasesandorganinjuries.TherearealsofourclinicalstudiesthattestMSCbasedtherapiesinpatientswithcancer.TheroleofMSCsintissueregenerationandcellularhomeostasisisbestexemplifiedinwoundhealing,acomplexprocessthatinvolvesmodulationoftissueinflammation,regulationofcellularproliferation,anddifferentiationandremodellingoftheinjuredtissue2,11.Duringthisprocess,inflammatorymediatorshavebeenshowntofacilitatetherecruitment,proliferationanddifferentiationofMSCs3,12.Uponmigratingspecificallytowounds,MSCsactivelyintegrateintodamagedtissuesandparticipateintissuerepair.Hence,MSCscanalterthelocalinflammatorymicroenvironment3,11andfacilitatewoundrepairactivitiesofintrinsictissuestemcellsbyproducingimmunoregulatoryfactors,growthfactorsandchemokines12.However,MSCsdonotalwayspromoteheal...
