Phenotype and function of human hematopoietic cells engrafting immune-deficient CB17-severe combined immunodeficiency mice and nonobese diabetic-severe combined immunodeficiency mice after transplantation of human cord blood mononuclear cells
Phenotype and function of human hematopoietic cells engrafting immune-deficient CB17-severe combined immunodeficiency mice and nonobese diabetic-severe combined immunodeficiency mice after transplantation of human cord blood mononuclear cells
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DOI：
10.1182/blood.v88.10.3731.bloodjournal88103731
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发表时间：
1996-11-15
期刊：
影响因子：
20.3
通讯作者：
Coulombel, L
中科院分区：
文献类型：
--
作者：
Pflumio, F;Izac, B;Coulombel, L
为了更好地了解移植人类细胞的嵌合免疫缺陷小鼠中干细胞功能的调节，以及体外和体内鉴定的祖细胞之间的亲缘关系，我们评估了静脉注射2至3 x 10(7)脐带血单核细胞后CB17-严重联合免疫缺陷（SCID）小鼠（34只小鼠，9次实验）骨髓中发现的造血祖细胞的不同区室。移植后 4 至 6 周，平均每四根长骨检测到 6.3 +/- 4 x 10(5) 个人类细胞，主要为粒单核细胞 (CD11b(+)) 和 B 淋巴细胞 (CD19(+)) 细胞。这些人类细胞中有 25% 表达 CD34 抗原，其中 90% 共表达 CD38 抗原，50% 共表达 CD19 抗原。静脉（IV）注射人细胞后3至10周，从嵌合CB17-SCID骨髓中分选人CD34（+）细胞和CD34（+）/CD38（-）细胞后，对祖细胞（克隆形成细胞和长期培养起始细胞[LTC-IC]）进行功能评估。与来自起始脐带血单核细胞的CD34(+)细胞中具有相似功能的细胞频率(分别为26%+/-7%和7.2%+/-5%)相比，集落形成细胞和LTC-IC的频率较低(CD34(+)部分中分别为4%和0.4%)。更令人惊讶的是，在从嵌合小鼠中分选的人CD34(+) CD38(-)级分中LTC-IC的频率也很低。这一观察结果的部分原因可能是CD34(+) CD19(+) B 细胞前体区室的扩张。尽管频率和绝对数量降低，但与输入 LTC-IC 相比，这些 LTC-IC 的分化能力（通过与鼠基质细胞共培养 5 周后的克隆形成后代输出来评估）是完整的。此外，在移植后 4 周研究的严重联合免疫缺陷 (SCID) 小鼠以及成人骨髓或脐带血悬浮液中，克隆祖细胞与 LTC-IC 之间的比率相似。使用非肥胖糖尿病 (NOD)-SCID 小鼠作为受体的实验中产生的结果表明植入水平较高，但克隆细胞或 LTC-IC 的分布没有变化。这些结果表明，在人类造血组织中经典定义的造血分化层次可以在免疫缺陷 SCID 或 NOD-SCID 小鼠中重建。 (C) 1996 年，美国血液学会。
In an attempt to understand better the regulation of stem cell function in chimeric immunodeficient mice transplanted with human cells, and the filiation between progenitor cells identified in vitro and in vivo, we assessed the different compartments of hematopoietic progenitors found in the marrow of CB17-severe combined immunodeficiency (SCID) mice (34 mice, 9 experiments) after intravenous injection of 2 to 3 x 10(7) cord blood mononuclear cells. On average 6.3 +/- 4 x 10(5) human cells were detected per four long bones 4 to 6 weeks after the transplant predominantly represented by granulomonocytic (CD11b(+)) and B lymphoid (CD19(+)) cells. Twenty five percent of these human cells expressed the CD34 antigen, of which 90% coexpressed the CD38 antigen and 50% the CD19 antigen. Functional assessment of progenitor cells (both clonogenic and long-term culture-initiating cells [LTC-IC]) was performed after human CD34(+) cells and CD34(+)/CD38(-) cells have been sorted from chimeric CB17-SCID marrow 3 to 10 weeks after intravenous (IV) injection of human cells. The frequency of both colony-forming cells and LTC-IC was low (4% and 0.4%, respectively in the CD34(+) fraction) when compared with the frequencies of cells with similar function in CD34(+) cells from the starting cord blood mononuclear cells (26% +/- 7% and 7.2% +/- 5%, respectively). More surprisingly, the frequency of LTC-IC was also low in the human CD34(+) CD38(-) fraction sorted from chimeric mice. This observation might be partly accounted for by the expansion of the CD34(+) CD19(+) B-cell precursor compartment. Despite their decreased frequency and absolute numbers, the differentiation capability of these LTC-IC, assessed by their clonogenic progeny output after 5 weeks in coculture with murine stromal cells was intact when compared with that of input LTC-IC. Furthermore the ratio between clonogenic progenitor cells and LTC-IC was similar in severe combined immunodeficiency (SCID) mice studied 4 weeks after transplant and in adult marrow or cord blood suspensions. Results generated in experiments where nonobese diabetic (NOD)-SCID mice were used as recipients indicate a higher level of engraftment but no change in the distribution of clonogenic cells or LTC-IC. These results suggest that the hierarchy of hematopoietic differentiation classically defined in human hematopoietic tissues can be reconstituted in immunodeficient SCID or NOD-SCID mice. (C) 1996 by The American Society of Hematology.