简介:目的:应用NOD/SCID小鼠构建人急性B淋巴细胞白血病-NOD/SCID小鼠模型。方法:采用4-5周龄NOD/SCID小鼠,每只小鼠尾静脉注射5×106个Nalm-6细胞,通过对小鼠一般状态,骨髓涂片,组织病理学检查等方法对白血病模型进行鉴定。结果:注射白血病细胞15d后,小鼠开始出现精神萎靡、食欲不振、皮毛皱缩、后肢无力和脊柱抬高等表现,骨髓涂片可见成团分布的白血病细胞,脾脏组织病理切片亦可见白血病细胞浸润。结论:通过尾静脉注射Nalm-6细胞于未经照射的NOD/SCID小鼠中可以成功建立全身播散的白血病模型,该模型的构建操作简单易行,成功率高,重复性好,为研究白血病发病机制及指导临床化疗方案设计提供了良好的研究平台。
简介:目的探讨CD47在急性髓细胞白血病NOD/SCID小鼠模型中的预后意义及靶向治疗的最佳策略。方法将分选的CD34+CD38-白血病干细胞(leukemiastemcells,LSCs)移植入NOD/SCID小鼠体内,建立小鼠急性单核细胞白血病模型;抗人CD47单克隆抗体单独或联合阿糖胞苷治疗白血病小鼠7~14d,并进行疗效分析。将LSCs与小鼠巨噬细胞在含抗CD47单克隆抗体的培养液中共培养,观察CD47对巨噬细胞吞噬LSCs能力的影响。结果THP-1细胞中存在CD34+CD38-LSCs,比例约为0.12%±0.06%,将分选后的CD34+CD38-LSCs(比例高达97.0%±1.7%)移植入NOD/SCID小鼠后成功建立白血病模型。体内实验表明,阿糖胞苷(7d)联合抗CD47单克隆抗体(14d)治疗后,白血病小鼠外周血和骨髓中CD33+CD45+白血病细胞下降最明显(P〈0.01),生存时间明显长于其它各组。体外共培养2h后,抗CD47单克隆抗体组吞噬指数(76.9%±12.2%)明显高于抗CD45单克隆抗体组(7.60%±2.4%,P〈0.01)。结论CD47高表达是急性髓细胞白血病的预后不良因素。阿糖胞苷联合抗CD47单克隆抗体可有效杀灭普通白血病细胞和白血病干细胞,对彻底治愈急性髓细胞白血病具有重要临床意义。
简介:Recombinanthumanprolactin(rhPRL)wasadministeredtohuPBL-SCIDmicetodetermineitseffectsonhumanimmunologicreconsfitutionandfunction.ThehuPBL-SCIDmiceweregiven10μgI.p.InjectionofrhPRLeveryotherdayforatotalof10injectionsafterhuPBLweretransferred.TheresultsdemonstratedthatrhPRLimprovedtheengraftmentoflymphocytesintothymus,lymphnodesandspleens,showingthatthecellularitiesoftheseorgansincreasedalthoughthecellularitiestendedtovarydependingonthedonor.TheamountsofhumanTcells(HLA-ABC+/CD3+)increasedgreatlyinthymus(14.2folds),spleen(4.16folds)andlymphnodes(40.18folds)afterrhPRLinjections.TheamountsofhumanBcells(HLA-ABC+/CD19+)alsoincreasedgreatlyinlymphnodes(42.5folds)andspleen(5.78folds).ThelymphnodecellsfromtherhPRL-treatedhuPBL-SCIDmiceweremoresensitivetoPHAstimulation([3H]thymidineincorporation).ThesupernatantofPHA-stimulatedPBLfromrhPRL-treatedhuPBL/SCIDchimerismcontainedmorecytokines(IFN-γandIL-2).Thenaturalcytotoxicityagainsthumansensitivetargetcells,K562cells,fromspleenandbonemarrowofhPBL/SCIDchimerismwassignificantlyenhancedbyrhPRLadministration.ThelymphnodecellswerestimulatedwithLPSinvitrofor3daysandthelymphocytesfromtherhPRL-treatedhuPBL-SCIDmiceweremoresensitivetomitogenstimulation.BothserumtotalIgGlevelandIgMlevelofrhPRL-treatedhuPBL/SCIDchimerismwereincreased,andevenwithoutDT-rechallengethebaselineofDT-specificIgGwaselevatedafterrhPRLtreatmentinhuPBL-SCIDmice.Thus,rhPRLstimulationpromotesreconstitutionofhumanimmunesysteminhuPBL-SCIDmice.
简介:Hepatocellularcarcinoma(HCC)isoneofthemostdeadlyhumancancers,butitisverydifficulttoestablishananimalmodelbyusingsurgicalspecimens.Inthepresentexperiment,histologicallyintactfreshsurgicalspecimensofHCCweresubcutaneouslytransplantedinnon-obesediabetic/severecombinedimmunodeficienccy(NOD/SCID)mice.Thebiologicalcharacteristicsoftheoriginalandthecorrespondingtransplantedtumorsandcelllineswereinvestigated.Theresultsshowedthat5newanimalmodelsand2primarycelllinesweresuccessfullyestablishedfromsurgicalspecimens.Hematoxylin-eosinstainingshowedthatxenograftsretainedmajorhistologicalfeaturesoftheoriginalsurgicalspecimens.Thetwonewcelllineshadbeencultivatedfor3yearsandsuccessivelypassagedformorethan100passagesinvitro.Themorphologicalcharacteristicsandbiologicfeaturesofthetwocelllinesweregeneticallysimilartotheoriginaltumor.Thesubcutaneoustransplantanimalmodelswithhistologicallyintacttumortissueandprimarycelllinescouldbeusefulforinvivoandinvitrotestingofanti-cancerdrugsandbeidealmodelstostudyvariousbiologicfeaturesofHCC.