急性淋巴细胞白血病CD34+CD38-细胞在NOD/SCID小鼠体内的自我更新与增值能力

摘要

Objective To explore the feasibility of establishing mouse model of leukemia by transplantion of human acute lymphoblastic leukemia (ALL) CD34+ CD38- cells into immunodeficient (NOD/SCID) mice, and to study the capability of self-renewal and proliferation in the mice. Methods The CD34+ CD38- cells were isolated from ALL patients and then identified, and the CD34- CD38+ cells were used as control. These cells were transplanted into sublethally irradiated NOD/SCID mice by tail-vein injection of 10 cells per recipient. The changes of peripheral blood were monitored continuously , and histopathological examination of the bone marrow, spleen and liver was performed in each death or dying mouse. Results The number of leukocytes in mouse peripheral blood was increased after inoculation of CD34+ CD38- or CD34- CD38+ cells at 4 weeks, peaked at 8 weeks up to 15 × 109～20 × 109/L, and also increased the number of original and blast lymphocytes. There were mainly increased the number of the original and blast lymphocytes (40% ) in the bone marrow, as well as the leukemic cells infiltrating in the spleen and liver of CD34 ' CD38 ~ mice, which was more obvious than that of the control CD34- CD38+ mice. Conclusions CD34+ CD38- cells from ALL patients can be successfully transplanted into NOD/SCID mice to induce leukemia, indicating that the CD34+ CD38- cells have the capability of self-renewal and proliferation. This model can be used as an important and useful tool for studies on leukemia-initiating cells.%目的 探索急性淋巴细胞白血病(ALL)患者CD34+ CD38-细胞移植到NOD/SCID小鼠体内建立白血病的可行性、自我更新与增殖潜能.方法 分选并鉴定ALL患者骨髓CD34+ CD38-细胞及对照CD34- CD38+细胞后,经尾静脉分别注射104个细胞于亚致死剂量射线照射的NOD/SCID小鼠体内,连续监测小鼠状态以及外周血血象改变,对濒死或死亡小鼠进行骨髓检查、肝脾病理学检查.结果 接种从ALL患者分选的CD34+ CD38-细胞到NOD/SCID小鼠体内后4周,小鼠外周血白细胞上升,到8周左右达高峰,约15×109～20× 109/L,原始及幼稚淋巴细胞明显增多.骨髓象显示以原始及幼稚淋巴细胞增生为主,约为40％,且肝脾组织也有白细胞浸润,明显高于接种了对照组CD34- CD38+细胞的NOD/SCID小鼠.结论 ALL患者CD34+CD38-细胞可以成功移植NOD/SCID 小鼠,在小鼠体内增殖形成白血病,说明该群细胞具有自我更新和增殖的潜能,可作为探索白血病起始细胞研究的重要载体.