人离体骨肉瘤组织血管噬菌体肽库筛选模型的建立及其意义

目的建立人离体骨肉瘤血管亲和筛选模型。方法(1)建立模型。术前对患肢局部行数字减影造影检查,标记肿瘤固有动脉大致走行,术后小心修剪,并连接类似于Langendorff的灌流装置,监控模型血管内的pH值、温度、氧分压等;(2)对噬菌体十二肽库进行筛选。结果28例骨肉瘤离体标本均建模成功,可直接用于灌流实验,并筛选出具有较高特异性的亲和短肽(基序为RLTR),各项指标显示离体骨肉瘤较好模拟了人体内的环境。结论建立人离体骨肉瘤血管亲和筛选模型是可行的,可直接用于对噬菌体随机肽库的亲和筛选,为骨肉瘤的靶向化疗提供参考。

Establishment of biopanning model of phage display peptide library in the blood vessels of excised human osteosarcoma vasculature and its significance

Objective To establishan in vivo biopanningmodelof phagedisplaypeptidelibraryin the bloodvessels containedin surgicallyremovedhumanosteosarcoma.Method In28patientswithosteosarcoma,digitalsubtraction angiography(DSA)of theinvolvedlimbwas performedpreoperativelyto understandtheapproximatestatusof thearteriesin thetumors.Thetumorswerethensurgicallyremovedandcarefullytrimmed,perfusedviaa simulatedLangendorffperfusion apparatuswiththeindexesas thepHvalue,temperatureandO 2 partialpressuremonitoredinthebloodvessels.A12-meres phagedisplaypeptidelibrarywas biopannedto isolatepeptidescapableof homingspecificallyto theexcisedosteosarcoma.Results In vivo biopanningmodelsweresuccessfullyestablishedin alltheexcisedtumors,whichcouldbe directlyusedin perfusionexperimentandtheindexesmonitoredinthebloodvesselsinthetumorswerecomparableto thoseof livingtissues.Somehigh-affinitypeptidesspecificto thebloodvesselsinosteosarcomawereobtainedwiththemotifof RLTR.Conclusion In vivo biopanningmodelsimulatingtheLangendorffperfusionapparatuscanbe easilyestablishedwhichis instrumentalfor theapplicationof phagedisplaytechnologyin humanlivingtissuesandmayfacilitatethestudyof targetedchemotherapyof osteosarcoma.