叶酸预处理髏下脂肪垫来源间充质干细胞来源的外泌体调控巨噬细胞极化

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Abstract：ObjectiveToevaluatetheeffectofexosomesderivedfromfolicacid （FA）-treatedinfrapatelarfatpadmesenchymal stemcells （IPFP-MSCs）onM1andM2polarizationof macrophagesinvitro.Methods Infrapatellarfatpadtisueswere obtained fromsurgicalpatients withoutkneeosteoarthritistoisolate IPFP-MSCs.The exosomes wereextractedfromthecell cultureswithorioutFAtreamentandidentifedbytransisioneleronicosoyEM，NandWestebloing. RAW264.7celswereinducedwithlipopolysaccharide（LPS）andincubatedwithexosomesfromFA-treatedoruntreatedIFPMSCs for 12h， andExos uptake was observed using confocal microscopy.The changes in expression levels of IL-1β，IL-6，TNF- ⋅α， iNOS，ARG1，MRC1，and CD206 in the macrophageswere detected using qRT-PCR，ELISA，flow cytometryand immunofluorescence staining.ResultsTheexosomes derivedfrom IPFP-MSCsshowedatypicalcupshape，werepositivefor CD9 and CD81，and couldbeuptaken by macrophages.In LPS-induced macrophages， incubation with exosomes from FAtreated IPFP-MSCssignificantlydecreased theexpressionsofIL-1β，IL-6， TNF- ⋅α， andNOs2，and increased the expressionsof ARG1and MRC1.Treatmentof themacrophages withexosomesfromFA-treated IPFP-MSCs significantlylowered CD86- positive cellprenageincrased-psitivecellsndtD/8atio，oweedcellarexprionofiad enhancedtheexpressionof CD206.Conclusion Exosomes fromFA-treatedIPFP-MSCspromotesM2 polarizationof macrophagesmoreefectivelythanexosomesfromunmodified IPFP-MSCs，suggestinganewexosomemodificationstrategy fortargeted treatmentofkneeosteoarthritis.

Keywords： folicacid; macrophage;exosomes; mesenchymal stem cells; osteoarthritis

骨关节炎（OA）是一种以关节软骨退行性变为主要特征的慢性进行性骨关节疾病，常伴有关节软骨下骨的硬化、骨赘形成、滑膜炎症反应以及关节结构破坏。（剩余18439字）