Strokeistheleadingcauseofadult-onsetdisabil-ityworldwide1.Mostsurvivorsofstrokeexperiencesomedegreeofspontaneousfunctionalrecovery,buttheregainoffunctiontendstobemodestandisofteninsufficientforsurvivorstobeindependentintheirdailylives.Consequently,disabilityafterstrokeimposesmanysocialandeconomicburdensonsoci-ety.Similarly,peoplewithtraumaticbraininjury(TBI)canexperiencespontaneousrecovery,butmanyareleftpermanentlydisabled,andnocurrentmedicalinterven-tioncanaidorimproveuponspontaneousrestorationofneurologicalfunction.Patientswhosurviveastrokeoftenimproverapidlyinthefollowingweeks(theacutephase),afterwhichtheirrecoveryslowsbutcancontinueformonths(thechronicphase)2.Thisspontaneousimprovementofneurologi-calfunction,whichisalsoobservedafterTBI,suggeststhatlimitedremodellingcanoccurintheadultbraintocompensateforinjuryandlossoftissue.Long-termneurologicalrecoveryisthoughttodependonremodel-lingofneuronalcircuitryinhealthytissuetocompensatefordeadanddamagedtissuethatisnotrecoverable.Forexample,inrodents,spontaneousremodellingofaxonsafterexperimentalischaemicstrokehasbeenobservedforatleast8weekswithoutanyintervention,andthisremodellingwasnecessaryforneurologicalrecovery3.Inthiscontext,apossibletherapeuticstrategytoimproverecoveryfrombraininsultssuchasstrokeandTBIisamplificationofintrinsicrestorativeprocessesbytargetingintactCNStissuetopromoteneuriteremod-ellinginthebrainandspinalcord,angiogenesisatthesiteofdamage,andfunctionalrestorativechangesintheglia(astrogliosis,oligodendrogenesisandinductionofareparativemicroglialphenotype).Initialattemptsatsuchastrategywerecell-basedtherapies,particularlywithmesenchymalstromalcells(MSCs)derivedfrombonemarrow4–8.Thisapproachhasprovedtobesafeandhasimprovedrecoveryofneuro-logicalfunctioninanimalmodels;early-phaseclini-calevidenceforMSCtherapyisalsopromising7,9.Therationaleforsuchcell-basedtherapieswasthereplace-mentofdeadneuronsbydifferentiationofgraftedMSCs,butoverwhelmingevidencefrompreclinicalstudiesdemonstratesthatMSCtherapyandoth...
