CellStemCellPerspectiveMesenchymalStromalCells:ClinicalChallengesandTherapeuticOpportunitiesJacquesGalipeau1,3,*andLucSense´be´2,3,*1DepartmentofMedicineandCarboneCancerCenter,UniversityofWisconsininMadison,Madison,WI,USA2UMR5273STROMALabCNRS/EFS/UPS–INSERMU1031,Toulouse,France3Theseauthorscontributedequally*Correspondence:jgalipeau@wisc.edu(J.G.),luc.sensebe@efs.sante.fr(L.S.)https://doi.org/10.1016/j.stem.2018.05.004Mesenchymalstromalcells(MSCs)havebeenthesubjectofclinicaltrialsformorethanageneration,andtheoutcomesofadvancedclinicaltrialshavefallenshortofexpectationsraisedbyencouragingpre-clinicalan-imaldatainawidearrayofdiseasemodels.InthisPerspective,importantbiologicalandpharmacologicaldisparitiesinpre-clinicalresearchandhumantranslationalstudiesarehighlighted,andanalysesofclinicaltrialfailuresandrecentsuccessesprovidearationalpathwaytoMSCregulatoryapprovalanddeploymentfordisorderswithunmetmedicalneeds.Mesenchymalstromalcells(MSCs)werefirsttestedasacellularpharmaceuticalagentinhumansubjectsin1995byHillardLazarus(Lazarusetal.,1995)andhavesincebecomethemostclinicallystudiedexperimentalcelltherapyplatformworldwideforwhichthereisnomarketingapprovalintheUnitedStates(Fungetal.,2017).Theenthusiasmforthesemostlyearly-phaseclinicaltrialsreflectstheconsiderableeasefortheenthusiasttomanufactureculture-adaptedMSCsfromreadilyaccessibletis-suesourcedfromnormalvolunteersandtheuseoftissueculturetechniquesdatingbackmorethanaquartercentury.IntheUnitedStatesinparticular,industrialsponsorshaveledvirtuallyalladvancedphaseIIIclinicaltrialsofMSCs,andthefieldasawholehasbeenseverelycriticizedforitsill-informedirrationalexuberance(Biancoetal.,2013).ThiscriticismoftenreflectsangstarisingfromtheegregiouslypredatorybusinessactivitiesofunregulatedstemcellclinicsintheUnitedStatesandworld-wide,ridingtheunprovenpromiseofregenerativetherapies,includingMSCs,asacure-all(TurnerandKnoepfler,2016).TheTravailsofMSCMarketingApprovalWorldwide:TheMSCsforGvHDParadigmMSCshavesecuredconditionalapprov...
