CAJ | 학술논문

目的利用人多发性骨髓瘤(MM)原代细胞在非肥胖糖尿病/重症联合免疫缺陷(NOD/SCID)小鼠中建立人MM异种移植模型.方法将2例MM终末期患者骨髓或外周血单个核细胞(MNC)悬液通过尾静脉分别输注给3只NOD/SCID小鼠.每周称量体重,移植2周后以流式细胞术(FCM)检测小鼠外周血中CD45+细胞百分比.当小鼠出现苍白、竖毛、精神萎靡或体重下降20％时,取小鼠脾脏及肝脏行组织病理学检查,FCM检测外周血、骨髓、脾脏和淋巴结细胞悬液中CD45+ CD38+细胞的百分比.结果来源于病例1和病例2的MNC移植小鼠的平均体重分别自输注MM原代细胞第7周和第5周后开始下降；以对照组小鼠的单个核细胞做阴性设门,分别于移植(26±4)d和(16±4)d后,在病例1细胞来源组和病例2细胞来源组的小鼠外周血中检测到人CD45+ CD38+细胞,且其比例随时间延长而逐渐增高,实验终点时分别达(16.2±3.0)％和(31.3±3.5)％；组织病理大体形态观察发现小鼠脾脏、肝脏及淋巴结均不同程度增大,镜下可见典型的恶性浆细胞浸润；FCM检查骨髓、淋巴结和脾脏细胞表面标志,均发现一群人源CD45+ CD38+细胞.结论成功建立了人MM原代细胞异种移植的免疫缺陷小鼠模型.
목적 이용인다발성골수류(MM)원대세포재비비반당뇨병/중증연합면역결함(NOD/SCID)소서중건립인MM이충이식모형.방법 장2례MM종말기환자골수혹외주혈단개핵세포(MNC)현액통과미정맥분별수주급3지NOD/SCID소서.매주칭량체중,이식2주후이류식세포술(FCM)검측소서외주혈중CD45+세포백분비.당소서출현창백、수모、정신위미혹체중하강20％시,취소서비장급간장행조직병이학검사,FCM검측외주혈、골수、비장화림파결세포현액중CD45+ CD38+세포적백분비.결과 래원우병례1화병례2적MNC이식소서적평균체중분별자수주MM원대세포제7주화제5주후개시하강；이대조조소서적단개핵세포주음성설문,분별우이식(26±4)d화(16±4)d후,재병례1세포래원조화병례2세포래원조적소서외주혈중검측도인CD45+ CD38+세포,차기비례수시간연장이축점증고,실험종점시분별체(16.2±3.0)％화(31.3±3.5)％；조직병리대체형태관찰발현소서비장、간장급림파결균불동정도증대,경하가견전형적악성장세포침윤；FCM검사골수、림파결화비장세포표면표지,균발현일군인원CD45+ CD38+세포.결론 성공건립료인MM원대세포이충이식적면역결함소서모형.
Objective To establish xenotransplated mouse model by non-obese diabetic/severe combined immunodeficiency (NOD/SCID) mice with primary myeloma cells.Methods The model of xenograft was established in NOD/SCID mice by tail vein injection of mononuclear cells from two end stage multiple myeloma patients,three mice were inoculated for each patient.Mice were monitored weekly for body weight.Two weeks later,the human CD45 + cells from peripheral blood of mice were evaluated by flow cytometry (FCM).The experiment endpoint was body weight loss up to 20％ or had pale,vertical hair and listlessness,then spleen and liver were studied by histologic analysis,the human CD45 + CD38 + cells from spleen,lymph node,peripheral blood and bone marrow were evaluated by FCM.Results Body weight of mice in group patient 1 and group patient 2 decreased seven and five weeks after inoculation respectively; the human CD45 +CD38 + cells appeared in the peripheral blood (26 ±4) and ( 16 ±4) days after inoculation in group patient 1 and group patient 2 respectively,and increased by time,reaching (16.2 ± 3.0)％ and (31.3 ± 3.5 )％,respectively at the endpoint; the spleen,liver and lymph node of both groups enlarged,the typical malignant plasma cells were observed in them.The human CD45 + CD38 + cells were detected in spleen,lymph node and bone marrow by FCM.Conclusion Our study successfully established a NOD/SCID mouse model xenotransplated with human primary myeloma cells.