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本研究旨在应用NOD/SCID/IL2rγnull新生小鼠建立人急性B淋巴细胞白血病(B-ALL)的异种移植模型。NOD/SCID/IL2rγnull新生期(出生48 h之内)小鼠经亚致死剂量(100 cGy)137Cs全身照射后,由面静脉输注FACSAria流式细胞仪分选纯化的B-ALL患者骨髓CD3-CD4-CD8-CD34+CD19+细胞,于移植后8-12周用流式细胞术检测受鼠外周血、骨髓和脾脏中人源细胞的植入水平及其免疫表型,并通过HE染色评价人源B-ALL细胞在受鼠各组织器官中的迁移浸润能力。结果表明,在接受B-ALL患者CD34+CD19+细胞移植的受鼠外周血、骨髓和脾脏细胞中,不仅检测到了不同程度的人源B-ALL(huCD45+CD19+)细胞的植入〔(83.36±10.05)%,(93.88±5.05)%,(88.31±5.01)%〕,而且植入细胞具有与B-ALL患者相似的细胞形态和免疫表型特征。此外,人源B-ALL细胞广泛迁移浸润到受鼠的肝脏、肺脏、肾脏和脑等组织器官中。结论:NOD/SCID/IL2rγnull新生小鼠模型能够支持B-ALL患者CD34+CD19+细胞的高水平植入,是对人B-ALL进行体内功能性研究的新型异种移植模型。
This study aimed to establish a xenograft model of human acute lymphoblastic leukemia (B-ALL) using NOD / SCID / IL2rγnull newborn mice. NOD / SCID / IL2rγnull After neonatal (within 48 hours of birth) mouse sublethal dose (100 cGy) of 137Cs whole body irradiation, the BAC of B-ALL patients were infiltrated with FACSAria flow cytometry by surface venous infusion. CD4-CD8-CD34 + CD19 + cells. The levels of human umbilical cord blood cells and their immunophenotypes in peripheral blood, bone marrow and spleen of mice were detected by flow cytometry 8-12 weeks after transplantation and evaluated by HE staining Migration of B-ALL cells in tissues and organs of affected mice. The results showed that not only different degrees of human B-ALL (huCD45 + CD19 +) cells were implanted in the peripheral blood, bone marrow and spleen cells of recipients receiving B-ALL from CD34 + CD19 + cells [(83.36 ± 10.05)%, (93.88 ± 5.05)%, (88.31 ± 5.01)%, respectively). Moreover, the implanted cells had similar cell morphology and immunophenotypic characteristics as B-ALL patients. In addition, human B-ALL cells are widely migrated and infiltrated into the tissues and organs of the liver, lung, kidney and brain of the mouse. CONCLUSIONS: The NOD / SCID / IL2rγnull neonatal mouse model is capable of supporting high levels of CD34 + CD19 + cells in B-ALL patients and is a novel xenograft model for in vivo functional studies of human B-ALL.