Human short-term repopulating stem cells are efficiently detected following intrafemoral transplantation into NOD/SCID recipients depleted of CD122+ cells
Human short-term repopulating stem cells are efficiently detected following intrafemoral transplantation into NOD/SCID recipients depleted of CD122+ cells
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DOI：
10.1182/blood-2005-03-1081
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发表时间：
2005-08-15
期刊：
影响因子：
20.3
通讯作者：
Dick, JE
中科院分区：
文献类型：
--
作者：
McKenzie, JL;Gan, OI;Dick, JE
非肥胖糖尿病/严重联合免疫缺陷（NOD/SCID）异种移植模型已成为广泛使用的人类造血干细胞检测方法；然而，仍然存在限制植入的障碍。我们之前在NOD/SCID小鼠中直接经股注射发现了短期的SCID再生细胞（SRC），而其他研究则在NOD/SCID小鼠中发现了类似的SRC，这些小鼠使用的是自然杀伤（NK）细胞活性耗尽的NOD/SCID小鼠。为了确定最有效检测短期src的模型，我们比较了6种不同异种移植模型中的人类移植：NOD/SCID- β 2-微球蛋白缺失小鼠，抗cd122（白细胞间素-2受体β [IL-2R β]）处理或未处理的NOD/SCID小鼠，每只小鼠通过静脉或静脉注射给予移植。在移植后2周和6周，经静脉注射抗cd122处理的NOD/SCID小鼠的人细胞植入量最高。这些对SRC检测的修改改进了对人类干细胞的检测，并证明CD122（+）细胞为干细胞植入提供了屏障，这一发现具有潜在的临床意义。
The nonobese diabetic/severe combined immune deficiency (NOD/SCID) xenotransplantation model has emerged as a widely used assay for human hematopoietic stem cells; however, barriers still exist that limit engraftment. We previously identified a short-term SCID-repopulating cell (SRC) following direct intrafemoral injection into NOD/SCID mice, whereas others characterized similar SRCs using NOD/SCID mice depleted of natural killer (NK) cell activity. To determine the model that most efficiently detects short-term SRCs, we compared human engraftment in 6 different xenotransplantation models: NOD/SCID-beta 2-microglobulin-null mice, anti-CD122 (interleukin-2 receptor beta [IL-2R beta])-treated or unmanipulated NOD/SCID mice, each given transplants by intravenous or intrafemoral injection. Human cell engraftment was highest in intrafemorally injected anti-CD122-treated NOD/SCID mice compared to all other groups at 2 and 6 weeks after transplantation. These modifications to the SRC assay provide improved detection of human stem cells and demonstrate that CD122(+) cells provide barriers to stem cell engraftment, a finding with potential clinical relevance.