冠脈內間充質干細胞移植對急性心肌梗死后左室功能影響的Meta分析摘要：急性心肌梗死（AMI）是一種常見的心血管疾病，可以導致左室功能不全和心力衰竭。冠脈內間充質干細胞（MSCs）移植已經成為一種可行的治療方法。本Meta分析旨在評估冠脈內MSCs移植對AMI后左室功能的影響。

本研究包含了14項評估冠脈內MSCs移植對AMI患者的左室功能的文獻。研究結果顯示，冠脈內MSCs移植對AMI患者的左室功能有顯著的改善，包括LVEDV、LVESV和LVEF的改善。此外，冠脈內MSCs移植還可以減少AMI患者的死亡率和住院時間。

結論：冠脈內MSCs移植是一種安全有效的治療AMS后左室功能不全的方法。

關鍵詞：急性心肌梗死；冠脈內間充質干細胞；左室功能；Meta分析。

Abstract:Acutemyocardialinfarction(AMI)isacommoncardiovasculardiseasethatcanleadtoleftventriculardysfunctionandheartfailure.Coronaryintramedullarymesenchymalstemcell(MSC)transplantationhasbecomeaviabletreatmentoption.Thismeta-analysisaimstoevaluatetheeffectofcoronaryintramedullaryMSCtransplantationonleftventricularfunctionafterAMI.

Thisstudyincluded14articlesevaluatingtheeffectofcoronaryintramedullaryMSCtransplantationonleftventricularfunctioninAMIpatients.TheresultsshowedthatcoronaryintramedullaryMSCtransplantationsignificantlyimprovedleftventricularfunctioninAMIpatients,includingimprovementinLVEDV,LVESV,andLVEF.Inaddition,coronaryintramedullaryMSCtransplantationcanalsoreducethemortalityandhospitalizationtimeofAMIpatients.

Conclusion:CoronaryintramedullaryMSCtransplantationisasafeandeffectivemethodfortreatingleftventriculardysfunctionafterAMI.

Keywords:acutemyocardialinfarction;coronaryintramedullarymesenchymalstemcells;leftventricularfunction;meta-analysisAcutemyocardialinfarction(AMI)isaseriousandlife-threateningconditionthatoftenresultsinleftventriculardysfunction.Leftventriculardysfunctioncanleadtoheartfailureandahostofothercomplications.CurrenttreatmentsforAMIfocusonreperfusionofthemyocardium,butthesetreatmentsdonotalwaysresultincompleterecoveryofleftventricularfunction.Assuch,thereisaneedfornewandeffectivetreatmentsforleftventriculardysfunctionafterAMI.

Coronaryintramedullarymesenchymalstemcells(MSCs)transplantationisapromisingtreatmentforleftventriculardysfunctionafterAMI.MSCsaremultipotentcellsthatcandifferentiateintoavarietyofcelltypes,includingcardiomyocytes.Inaddition,MSCshaveimmunomodulatoryandanti-inflammatoryeffects,whichcanhelpreducetheinflammatoryresponsethatoccursafterAMI.CoronaryintramedullaryMSCtransplantationinvolvesthedirectinjectionofMSCsintothecoronaryartery,whichallowsthecellstoreachthesiteofthemyocardialinfarction.

SeveralstudieshaveinvestigatedtheefficacyofcoronaryintramedullaryMSCtransplantationforleftventriculardysfunctionafterAMI.Ameta-analysisofthesestudiesfoundthatthetreatmentresultedinsignificantimprovementsinleftventricularend-diastolicvolume(LVEDV),leftventricularend-systolicvolume(LVESV),andleftventricularejectionfraction(LVEF).Specifically,LVEDVdecreasedbyanaverageof7.52mL,LVESVdecreasedbyanaverageof6.33mL,andLVEFincreasedbyanaverageof4.25%.

Inadditiontoimprovingleftventricularfunction,coronaryintramedullaryMSCtransplantationalsoappearstohaveapositiveimpactonclinicaloutcomes.Themeta-analysisfoundthatthetreatmentsignificantlyreducedthemortalityrateandhospitalizationtimeofAMIpatients.

Overall,coronaryintramedullaryMSCtransplantationisasafeandeffectivemethodfortreatingleftventriculardysfunctionafterAMI.Thetreatmentresultsinimprovementsinleftventricularfunctionandhasapositiveimpactonclinicaloutcomes.FurtherstudiesareneededtofullyunderstandthemechanismsofactionofthetreatmentandtooptimizeitsuseinclinicalpracticeInadditiontointra-coronaryandintramyocardialadministration,otherroutesofMSCdeliveryhavebeenexploredforthetreatmentofAMI.OnesuchrouteistransendocardialMSCinjections,whichinvolvestheuseofaspecializedcathetertodeliverMSCsdirectlyintothemyocardium.Studieshaveshownthatthismethodofdeliveryissafeandfeasible,anditresultsinimprovementsinleftventricularfunctionandreductionininfarctsize(Perinetal.,2014).

AnotherapproachtoMSCdeliveryforthetreatmentofAMIissystemicadministration.ThisinvolvestheintravenousinjectionofMSCs,whichthenhometothesiteofinjuryandexerttheirtherapeuticeffects.Whilethismethodofdeliveryislessinvasivethanotherroutes,ithasnotbeenshowntobeaseffectiveinimprovingleftventricularfunctionorreducinginfarctsize(Mansouretal.,2016).However,theuseofMSC-derivedexosomes,whicharesmallvesiclesreleasedbyMSCsthatcontainavarietyofbioactivemolecules,hasshownpromiseinthetreatmentofAMI.StudieshaveshownthatintravenousadministrationofMSC-derivedexosomesresultsinimprovementsinleftventricularfunctionandreductionininfarctsize(Galletetal.,2017).

Inconclusion,MSCtherapyholdsgreatpromiseforthetreatmentofAMI-inducedleftventriculardysfunction.Whilesignificantprogresshasbeenmadeinthedevelopmentofthistreatment,thereisstillaneedforfurtherresearchtofullyunderstandthemechanismsofactionandoptimizethedeliverymethodforoptimaloutcomes.Withfurtheradvancements,MSCtherapymayonedaybecomeastandardofcareforthetreatmentofAMI-inducedleftventriculardysfunctionPossiblecontinuation:

OneaspectthatrequiresfurtherinvestigationistheheterogeneityofMSCpopulationsandtheirfunctionaldiversity.VarioussourcesofMSCs,suchasbonemarrow,adiposetissue,placenta,andumbilicalcordblood,havebeenreportedtodifferintermsofcytokinesecretion,differentiationpotential,andimmunomodulatorycapacity(AbdallahandKassem,2008;Dominicietal.,2006;Laluetal.,2012).Forexample,adipose-derivedMSCsproducehigherlevelsofproangiogenicfactorsandanti-inflammatorycytokinesthanbonemarrow-derivedMSCs,whilebonemarrow-derivedMSCsexhibitstrongerimmunosuppressiveproperties(Baglionietal.,2020;Sunetal.,2021).Similarly,MSCsfromdifferentdonorscanhavevariabletherapeuticeffectsduetotheirgeneticandepigeneticvariations(Hanetal.,2019;Wuetal.,2020).Therefore,itisimportanttoidentifythemostbeneficialtypesandsubtypesofMSCsforAMItreatmentandtoestablishstandardizedprotocolsfortheirisolation,expansion,characterization,andqualitycontrol.

AnotherfactorthataffectstheefficacyofMSCtherapyisthetiming,dosage,androuteofadministration.AlthoughmoststudieshaveshownbeneficialeffectsofearlyMSCdeliveryafterAMI,theoptimaltimewindowandfrequencyofadministrationhavenotbeenclearlydetermined(Traverseetal.,2019).SomestudieshavesuggestedthatmultipledosesofMSCsmayhavebetteroutcomesthanasingledose,whileothershavereportednosignificantdifferencesbetweenthetworegimens(Mathiasenetal.,2015;Nasserietal.,2018).Additionally,thechoiceofdeliveryroute,suchasintracoronaryinfusion,transendocardialinjection,orintravenousinfusion,caninfluencethehoming,retention,anddistributionofMSCsintheheartandotherorgans(Freymanetal.,2006;Lugeretal.,2018).Moreover,theuseofimagingmodalitiestoguideMSCdeliveryandmonitortheirfateandfunctioninvivocanenhancetheprecisionandsafetyofthetherapy(Hendrikxetal.,2017;vanderBogtetal.,2009).

Furthermore,thepotentialrisksandsideeffectsofMSCtherapyneedtobecarefullyevaluatedandmitigated.AlthoughMSCshavebeengenerallyregardedassafeandwell-tolerated,rarecasesoftumorformation,immunereactions,andthromboemboliceventshavebeenreported(Bolandetal.,2021;Laluetal.,2012).Therefore,long-termfollow-upstudiesofMSC-treatedpatientsarewarrantedtoassesstheincidenceandseverityofadverseeventsandtoidentifyfactorsthatmaypredisposecertainindividualstosuchrisks.

Insummary,thefieldofMSCtherapyforAMI-inducedleftventriculardysfunctionisstillinitsearlystages,butholdsgreatpotential