Namikawa R, Ueda R, Kyoizumi S
New Enterprise Research Division, SyStemix Inc., Palo Alto, CA.
Blood. 1993 Oct 15;82(8):2526-36.
It has been shown previously that multilineage human hematopoiesis is maintained within human fetal bone marrow (BM) fragments implanted into severe combined immunodeficient (SCID) mice. We describe here an application of this animal model, the SCID-hu mouse, to the study of human myeloid leukemias. BM cells from 8 patients with various types of myeloid leukemias were injected directly into human bone grafts in the SCID-hu mouse. Cells from 7 patients grew in the human marrow without spreading to the mouse marrow. Cells from 6 of these patients were successfully transferred in vivo to secondary SCID-hu recipients. The surface phenotype and the cytologic features of the leukemia cells were conserved during passage in vivo. Thus, human myeloid leukemia cells could be reproducibly propagated in the human marrow environment in SCID-hu mice. The differentiation of promyelocytic leukemia cells in the SCID-hu mice was induced by all-trans retinoic acid, suggesting that the biologic features of the leukemia cells were maintained as well. Finally, evidence for a leukemic progenitor cell population in one case of acute myelogenous leukemia was provided with this system. This model may provide a useful tool for studying the biology of human myeloid leukemia as well as for evaluating new therapeutic modalities for myeloid leukemias.
先前已表明，将人胎儿骨髓（BM）片段植入严重联合免疫缺陷（SCID）小鼠体内可维持多谱系人类造血功能。我们在此描述这种动物模型——SCID-hu小鼠在人类髓系白血病研究中的应用。将8例患有各种类型髓系白血病患者的BM细胞直接注射到SCID-hu小鼠的人骨移植物中。7例患者的细胞在人骨髓中生长，未扩散至小鼠骨髓。其中6例患者的细胞在体内成功转移至二代SCID-hu受体。白血病细胞的表面表型和细胞学特征在体内传代过程中得以保留。因此，人类髓系白血病细胞可在SCID-hu小鼠的人骨髓环境中反复增殖。全反式维甲酸可诱导SCID-hu小鼠中的早幼粒细胞白血病细胞分化，这表明白血病细胞的生物学特性也得以维持。最后，该系统为一例急性髓性白血病中白血病祖细胞群体的存在提供了证据。该模型可能为研究人类髓系白血病的生物学特性以及评估髓系白血病的新治疗方法提供有用的工具。
