Human hematopoiesis in SCID mice implanted with human adult cancellous bone.
Human hematopoiesis in SCID mice implanted with human adult cancellous bone.
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DOI：
10.1182/blood.v88.6.1973.bloodjournal8861973
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发表时间：
1996-09
期刊：
影响因子：
20.3
通讯作者：
J. Sandhu;B. Clark;E. Boynton;H. Atkins;H. Messner;A. Keating;N. Hozumi
中科院分区：
文献类型：
--
作者：
J. Sandhu;B. Clark;E. Boynton;H. Atkins;H. Messner;A. Keating;N. Hozumi
研究了皮下植入 CB-17 scid/scid 小鼠体内的成人松质骨碎片的造血细胞的持久性。受体小鼠在植入前不接受预处理（对照组）或接受 3 Gy 全身照射和抗唾液酸 GM1 血清（ASGM1；预处理组）预处理。随后，在实验期间，对植入人骨的经过预处理的严重联合免疫缺陷 (SCID) 小鼠每 7 天注射一次 ASGM1。植入后 12 周，对来自预处理和对照动物组织的细胞进行流式细胞术检测，在小鼠脾脏（预处理动物和对照动物，分别为平均 7.8% 和 3.4% 阳性细胞）、骨髓（BM；平均分别为 16.5% 和 4.8% 阳性细胞）和血液（平均分别为 5.5% 和 < 2% 阳性细胞）和植入的人骨中检测到人 CD45+ 细胞（分别为 73% 和 8.9% 的阳性细胞）。第 12 周时，预处理小鼠的小鼠 BM 和一些脾脏中植入的人骨中含有人粒细胞巨噬细胞集落形成细胞 (GM-CFC) 和爆发形成单位红细胞 (BFU-E)。脾脏也有大量的人类 B 细胞和巨噬细胞浸润。在第 6 至 12 周期间，预处理动物中人 IgG 的平均血清水平为 14 微克/mL，而对照小鼠中的痕量水平 (< 1 微克/mL)。急性髓细胞白血病 (AML) 患者的骨骼也被植入经过预处理的 SCID 小鼠体内，并在 8 周时取出进行分析。植入前和植入样本的比较显示，原始组织学得到维持，并且在小鼠脾脏和BM中观察到大量人CD68+细胞浸润。在 SCID 小鼠中植入 AML 骨有助于分析原位 AML 细胞与白血病状态下基质细胞的相互作用，并且可以在该系统中测试针对 AML 的治疗，特别是在其他 BM 细胞存在的情况下选择性杀死 AML 细胞。此外，该模型不需要外源性施用细胞因子来维持正常或 AML 骨的人类造血功能。由于正常和患病成人骨骼的结构和功能均得到保留，因此该动物模型应有助于研究正常人类造血和造血系统恶性肿瘤。
The persistence of hematopoietic cells from human adult cancellous bone fragments implanted subcutaneously into CB-17 scid/scid mice was studied. Recipient mice received either no pretreatment (control group) or pretreatment with 3 Gy total-body irradiation and anti-asialo GM1 sera (ASGM1; pretreated group) before implantation. Pretreated severe combined immunodeficient (SCID) mice implanted with human bone were subsequently given ASGM1 every 7 days for the duration of the experiments. At 12 weeks postimplantation, flow cytometry of cells from pretreated and control animal tissues detected human CD45+ cells in the mouse spleen (mean, 7.8% and 3.4% positive cells, pretreated and control animals, respectively), bone marrow (BM; mean, 16.5% and 4.8% positive cells, respectively), and blood (mean, 5.5% and < 2% positive cells, respectively), and in the implanted human bone (73% and 8.9% positive cells, respectively). At 12 weeks, pretreated mice had human granulocyte-macrophage colony-forming cells (GM-CFC) and burst-forming units-erythrocyte (BFU-E) in the implanted human bone in the murine BM and in some of the spleens. The spleens also had extensive infiltration of human B cells and macrophages. Mean serum levels of human IgG in pretreated animals were 14 micrograms/mL during weeks 6 to 12, compared with trace levels (< 1 microgram/mL) in control mice. Bone from patients with acute myeloblastic leukemia (AML) was also implanted in pretreated SCID mice, and retrieved at 8 weeks for analysis. Comparison of preimplantation and implanted samples showed that the original histology was maintained, and massive infiltration of human CD68+ cells was observed in the mice spleens and BM. Implantation of AML bone in SCID mice facilitates analysis of in situ AML cell interaction with stromal cells in the leukemic state, and therapies against AML can be tested in this system, especially the selective killing of AML cells in the presence of other BM cells. Furthermore, this model requires no exogenous administration of cytokines to maintain human hematopoiesis with both normal or AML bone. Because the structure and function of both normal and diseased human adult bone is maintained, this animal model should facilitate investigation of both normal human hematopoiesis and hematopoietic malignancies.