CellStemCellReviewEngineeringStemandStromalCellTherapiesforMusculoskeletalTissueRepairClaudiaLoebel1andJasonA.Burdick1,*1DepartmentofBioengineering,UniversityofPennsylvania,Philadelphia,PA19104,USA*Correspondence:burdick2@seas.upenn.eduhttps://doi.org/10.1016/j.stem.2018.01.014Stemcellsandtissue-derivedstromalcellsstimulatetherepairofdegeneratedandinjuredtissues,moti-vatingagrowingnumberofcell-basedinterventionsinthemusculoskeletalfield.Recentinvestigationshaveindicatedthatthesecellsarecriticalfortheirtrophicandimmunomodulatoryroleincontrollingendog-enouscells.ThisReviewpresentsrecentclinicaladvanceswherestemcellsandstromalcellshavebeenusedtostimulatemusculoskeletaltissuerepair,includingdeliverystrategiestoimprovecellviabilityandretention.Emergingbioengineeringstrategiesarehighlighted,particularlytowardthedevelopmentofbioma-terialsforcapturingaspectsofthenativetissueenvironment,alteringthehealingniche,andrecruitingendog-enouscells.Musculoskeletaltissueinjuriesanddegenerationarecommonanddebilitatingforahighnumberofpatients(Brooks,2006).Un-fortunately,endogenousmusculoskeletaltissueregenerationislimitedinmanycasesandmaybeaffectedbyinflammationandthedegreeofdamage.Forexample,mostfracturesoflongboneshealspontaneously,whereaslargesegmentalde-fectsfailtoheal.Additionally,althougharticularcartilagehasalmostnointrinsicreparativepotential,tendonsandligamentsmayheal,butoftenwithinferiorproperties.Thehighprevalenceoftheseinjurieshasledtosignificantinvestmentinthedevelop-mentofnewtherapiestoenhancehealingandaugmentcurrentsurgicalinterventions.Oftenthegoalistomimicandrecapitulatethenaturalhealingcascadeanddevelopmentalprocessbytransplantationoftissue-specificstromalandprogenitorcellsorbyendogenousmanipulationtoenhancethenativerepairca-pacityofcells.Therehasbeenacontinuingincreaseinthenumberandtypeofstemandstromalcellsbeingpursuedinhumanclinicaltrialsfortreatmentofmusculoskeletalinjuries(Steinertetal.,2012).Mostapproachesinthisareaarebasedonexvivo-expandedmesenchymalstromalcel...
