Growth of human hematopoietic cells in immunodeficient mice conditioned with cyclophosphamide and busulfan.

Growth of human hematopoietic cells in immunodeficient mice conditioned with cyclophosphamide and busulfan.
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用环磷酰胺和白消安调节的免疫缺陷小鼠中人类造血细胞的生长。

DOI:
10.1002/stem.150314
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发表时间:
1997
期刊:
Stem cells (Dayton, Ohio)
影响因子:
--
通讯作者:
Hirst,JA
Hirst,JA
中科院分区:
--
文献类型:
--
作者:
Basch,RS;Quito,FL;Beh,J;Hirst,JA

文献摘要

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在用细胞毒药物丁硫丹和环磷酰胺制备的严重联合免疫缺陷小鼠中,人类造血细胞存活和增殖至少10周。在小鼠体内生长的人类细胞可以通过使用检测人类重复DNA的探针进行原位杂交或用抗人抗体(抗CD45和抗HLAI)染色来检测。白花丹/环磷酰胺处理的小鼠被注射了广泛的细胞剂量,从500万到5000万个普通骨髓细胞和200万到4000万个低密度骨髓细胞不等。分别于移植后1、3、5、7、10周处死动物。在许多动物身上发现了人类细胞,最早在移植后一周就能检测到。再繁殖的高峰是在两到五周,但在一些动物中,可以检测到长达10周的人类细胞。许多人类细胞表达高水平的血糖素,但没有发现成熟的人类红细胞。人类细胞在整个骨髓中分布不均匀。它们生长在骨盆下区域的小簇中。人类在小鼠体内的造血再繁殖的程度是非常不同的。在任何时候,在任何剂量下,所有的动物都不能实现再繁殖。人类生长因子的治疗对于人类造血细胞的存活是不必要的,但如果没有它们,正常的造血就不会发生。
Human hematopoietic cells survive and proliferate for at least 10 weeks in severe combined immunodeficient mice prepared with the cytotoxic drugs busulfan and cyclophosphamide. The human cells growing in the mice can be detected by in situ hybridization using a probe detecting human repetitive DNA or by staining the cells with antihuman antibodies (anti-CD45 and anti-HLA I). Busulfan/cyclophosphamide-treated mice were injected with a wide range of cell doses, ranging from 5 to 50 million unfractionated bone marrow cells and 2 to 40 million low density bone marrow cells. Animals were killed at 1, 3, 5, 7 and 10 weeks after transplantation. Human cells were found in many animals and could be detected as early as one week after transplantation. The peak of repopulation was at two to five weeks, but in some animals human cells could be detected for as long as 10 weeks. Many of the human cells expressed high levels of glycophorin, but mature human erythrocytes were not found.The human cells were not uniformly distributed throughout the marrow. They grew in small clusters in the subepiphyseal region. The extent of human hematopoietic repopulation in the mouse was extremely variable. At no time and at no dose was repopulation achieved in all of the animals. Treatment with human growth factors is not necessary for the survival of the human hematopoietic cells but, in their absence, normal hematopoiesis does not occur.