摘要
目的比较儿童急性淋巴细胞白血病(acute lymphoblastic leukemia,ALL)CD34+CD38-细胞群在非肥胖糖尿病(non obese diabetic,NOD)/重症联合免疫缺陷(severe combined immunodeficient,SCID)小鼠与在NOD/SCID基础上敲除IL-2Rγ链的小鼠(NOD scid gamma,NSG)体内的复制能力。方法采用免疫磁珠法分选ALL患儿骨髓CD34+CD38-细胞(作为阳性细胞)及其他各群细胞(CD34+CD38+、CD34-CD38-、CD34-CD38+,作为阴性对照细胞),经尾静脉分别注射于NOD/SCID或NSG小鼠体内,104个/只,连续监测小鼠的发病情况并记录小鼠生存时间;进行小鼠外周血白血病细胞计数及外周血、骨髓血涂片检查;将濒死小鼠处死后,取肝、脾组织,进行病理学检查。结果 CD34+CD38-细胞注射入小鼠体内后,NOD/SCID小鼠的存活期为56~150 d,NSG小鼠的存活期为13~120 d;NOD/SCID小鼠外周血白细胞数量缓慢升高直至死亡或处死,NSG小鼠外周血白细胞数量从第7天开始升高,至75 d左右达高峰;NOD/SCID小鼠和NSG小鼠分别于注射CD34+CD38-细胞3周和2周后外周血涂片可见白血病细胞,NSG小鼠外周血涂片发现更多的蓝染幼稚细胞;NSG小鼠骨髓涂片中发现更多的圆形、外源整齐、蓝色深染的幼稚细胞;NSG小鼠脾脏组织中有明显的炎细胞团块,且组织疏松,NOD/SCID小鼠脾脏组织中未发现明显的炎细胞团块,且组织相对致密,两种小鼠的肝脏组织中均未发现明显的炎细胞团块和组织结构改变。结论 ALL CD34+C38-细胞在NOD/SCID小鼠及NSG小鼠体内均能增殖复制出白血病,NSG小鼠复制白血病的时间更短,恶性程度更高,且白血病的复制过程更接近人类白血病的病理过程。本实验为白血病发病机理的研究和临床用药的评价提供了更好的载体。
Objective To compare the propagation abilities of childhood acute lymphoblastic leukemia （ALL） CD34＋ CD38-cell groups in non obese diabetic （NOD）/severe combined immunodefieient （SCID） and NOD seid gamma （NSG） mice. Methods CD34＋CD38- cell groups and other groups （CD3d＋CD83-, CD34-CD38- and CD34-CD38＋） groups as negative control were isolated from children with ALL with immunomagnetic microbeads, and transplanted into NOD/ SCID or NSG mice by tail vein injection, 104 cells for each. The onset of mice was monitored continuously, and the survival time as recorded. The peripheral blood leukemia cells of mice were counted, and the smears of peripheral and bone marrow were examined. The dying mice were killed, of which the liver and spleen tissues were subjected to histopathological examination. Results After injection with CD34＋CD38- cells, the survival period of NSG mice was 56 150 d, while that of NSG mice was 13 - 120 d. The count of leukocytes in peripheral blood of NOD / SCID mice increased slowly until death or being killed, while that in NSG mice increased starting from ？ d and reached a peak value about 75 d after injection. Leukemia cells were observed on peripheral blood smears of NOD /SCID mice 3 weeks and NSG mice 2 weeks after injection with CD34＋CD38- cells, while more blue-stained naive cells in NSG mice. More round naive cells with irregular borders, stained darkly blue, were observed on bone marrow smears of NSG mice. Obvious inflammatory cell blocks were observed in spleen tissue of NSG mice, while the tissue was loose. However, no obvious inflammatory cell blocks were observed in the spleen tissue of NOD / SCID mice, and the tissue was relatively dense. No obvious inflammatory cell blocks or structural change was observed in liver tissues of NOD/SCID and NSG mice. Conclusion Leukemia was induced by ALL CD34＋CD38- in NOD/SCID mice and NSG mice. However, the time for induction of leukemia in NSG mice was short, while the malignant grade leukemia was high, and the c
出处
《中国生物制品学杂志》
CAS
CSCD
2013年第12期1776-1780,共5页
Chinese Journal of Biologicals
基金
重庆市自然科学基金-杰出青年基金(2010BA5008)
