OpinionHeartFailureandAdiposeMesenchymalStemCellsKenichiMatsushita1,*Mesenchymalstemcells(MSCs)areconsideredapromisingcelltypeforthetreatmentofheartfailure(HF).Inparticular,MSCsinadiposetissuearebeingevaluatedasaneffectivetherapeutictool.However,adiposeMSCsareamajorsourceofadipocytegenerationandlinkedtoobesity,whichisanindependentriskfactorforHF.MSCsexpressallofthecomponentsoftherenin–angiotensinsystem(RAS),whichplaysapivotalroleinthepathophysiologyofHF.ThelocalRASalsoregulatesMSCadipogenesis,indicatingaconnectionbetweenMSC–adipogenesis–obesityandHF.ThisreviewexaminesevidenceofthecomplexrelationshipbetweenHFandadiposeMSCsanddiscusseshowtoexplorethisassociationforfavorabletherapeuticoutcomesforHF.TheComplicatedRelationshipbetweenHFandAdiposeMSCsHFisacomplexclinicalsyndromecausedbystructuraland/orfunctionalcardiacabnormalities[1,2].AlthoughHFisaheterogeneousconditionanditspathophysiologyisnotfullyunderstood,asignificantcontributionofneurohormonalactivationhasbeenidentified[1,3,4].Inparticular,theRAS(seeGlossary)playsacentralroleinthepathogenesisandprogressionofHF[3–6].Activationofthecirculatingand/ortissueRAScausessaltandwaterretention,vasoconstriction,andcardiacandvascularhypertrophy,fibrosis,andremodeling,aswellasenhancingthedeleteriouseffectsofotherneurohormonalsystemssuchasthesympatheticnervoussystem[4,6].HFisagrowinghealthburdenworldwide,anddespiteprogressinpharmacologicalanddevicetherapies,patientswithadvancedHFhavefewoptions[7–9].MechanicalcirculatorysupportandhearttransplantationarecurrentlythemaintreatmentstrategiesforseverelyprogressedHF,buttheyarerestrictedbypatienteligibility,donoravailability,andcost[7,8].Consequently,findingalternativetherapiesforHFisanimportantareaofresearch.CelltherapyusingMSCsisoneofthemostpromisingapproachesfortreatingHF,withmanyen-couragingresultsinpreclinicalandclinicalstudies[10,11].MSCsarenonhematopoietic,multipotentself-renewingcellswiththeabilitytodifferentiateintomultiplemesodermallineagecelltypesandtotransdifferentiat...
