HarnessingtheMesenchymalStemCellSecretomeforRegenerativeUrologyDanielZSun,MD1,2,3,BenjaminAbelson,MD1,2,3,PaurushBabbar,MD1,2,3,MargotSDamaser,PhD1,2,3,41DepartmentofUrology,GlickmanUrologicalandKidneyInstitute,ClevelandClinic,Cleveland,OH2ClevelandClinicLernerCollegeofMedicineatCaseWesternReserveUniversity,Cleveland,OH3DepartmentofBiomedicalEngineering,LernerResearchInstitute,ClevelandClinic,Cleveland,OH4AdvancedPlatformTechnologyCenter,LouisStokesClevelandVAMedicalCenter,Cleveland,OHAbstractTheextensivearsenalofbioactivemoleculessecretedbymesenchymalstemcells,alsoknownasthe“secretome”,hasdemonstratedconsiderabletherapeuticbenefitinregenerativemedicine.Thesecretomeasaninvestigativetreatmenthasenabledresearcherstoreplicatetheanti-inflammatory,angiogenic,andtrophiceffectsofstemcellswithouttheneedforthecellsthemselves.Thisreviewwilldiscusstherationale,mechanisms,andcurrentunderstandingsurroundingthemesenchymalstemcellsecretomeinurology.Wewillreviewrecentpre-clinicalstudiesutilizingthesecretomeforstressincontinence,renaldisease,bladderdysfunction,anderectiledysfunction.Finally,wewilldescribeproteomicmethodsusedtocharacterizethesecretomeandprovideinsightintofutureperspectivesregardingstemcellsandtheirsecretions.Keywordsmesenchymalstemcells;conditionedculturemedia;secretome;regenerativemedicine;urology1.IntroductionRecentinnovationsinstemcellresearchhaveunlockedthepotentialfortherapiesinregenerativeurology.Stemcellsareauniquecellpopulationduetotheirabilitytoself-renew,proliferate,anddifferentiateintomultipleterminalcelltypes.TheypossessuniqueCorrespondingAuthor:DanielZSun,GlickmanUrologicandKidneyInstitute,ClevelandClinic,9500EuclidAve,Cleveland,OH44195,Tel:(216)212-0725,sund4@ccf.org.AuthorcontributionsDr.Suncontributedtothemanuscript’sconceptionanddesign,drafting,writingandfinalrevisionsDrs.AbelsonandBabbarparticipatedinaspectsofthemanuscript’swritingandrevisionsDr.Damasercontributedtothedesign,revisions,editingandthefinalapprovalofthemanuscriptforsubmissionComp...