Hematopoietic progenitor stem cell homing in mice lethally irradiated with ionizing radiation at differing dose rates
Hematopoietic progenitor stem cell homing in mice lethally irradiated with ionizing radiation at differing dose rates
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DOI：
10.1667/rr3197
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发表时间：
2004-07-01
影响因子：
3.4
通讯作者：
DeWeese, TL
中科院分区：
文献类型：
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作者：
Collis, SJ;Neutzel, S;DeWeese, TL
最近有研究表明，去血统的小鼠造血干细胞移植后2天植入骨髓，能够长期植入和再生二次受体。我们感兴趣的是确定消融辐射剂量传递给小鼠的速度是否影响了谱系耗尽的干细胞归巢到骨髓和/或组织损伤部位。分离的、去血统的供体骨髓细胞被分离出来，并用膜染料PKH26标记。受体小鼠接受不同剂量率的11Gy电离辐射致死照射，并立即注射PKH26标记的祖细胞干细胞。除最低剂量率组外，所有受照小鼠归巢至骨髓的干细胞较未受照对照小鼠减少约五倍(P=0.014至0.025)。与未受照射的动物相比，归巢到脾的干细胞减少了五倍，尽管这在任何剂量率组中都没有统计学意义(P=0.072至0.233)。这种归巢差异不能用干细胞凋亡/坏死增加或非骨髓组织归巢到肠、肺或肝脏来解释。我们的研究表明，在辐射/移植后2天或5天，致死剂量全身辐射的剂量率不会增加造血祖干细胞归巢到骨髓、脾或早期辐射介导的组织损伤的部位。在未受辐射的对照组小鼠中观察到了更大的归巢，这一观察结果质疑了这样的概念，即充分的骨髓干细胞归巢需要辐射诱导的骨髓中形成空间。当然，对于用于这套实验的丰富的早期祖细胞造血干细胞来说。还需要进一步的实验来确定这些归巢细胞是否能够像在接受辐射的受者中那样，引起二次受者骨髓的长期植入/再繁殖。(C)2004年，由辐射研究学会提供。
It has recently been shown that specific lineage-depleted murine hematopoietic stem cells that home to the bone marrow 2 days after transplantation of ablated primary recipients are capable of long-term engraftment and repopulation of secondary recipients. We were interested in determining whether the rate at which the ablating radiation dose was delivered to the mice affected the homing of lineage-depleted stem cells to the bone marrow and/or sites of tissue damage. Fractionated, lineage-depleted donor marrow cells were isolated and labeled with the membrane dye PKH26. Recipient mice were lethally irradiated with 11 Gy ionizing radiation using varying dose rates and were immediately injected with PKH26-labeled progenitor stem cells. With the exception of the lowest dose-rate group, all irradiated mice had an approximately fivefold (P = 0.014 to 0.025) reduction in stem cell homing to the bone marrow compared to unirradiated control animals. A fivefold reduction of stem cell homing to the spleen compared to unirradiated animals was also observed, though this was not statistically significant for any dose-rate group (P = 0.072 to 0.233). This difference in homing could not be explained by increased stem cell apoptosis/necrosis or non-marrow tissue homing to the intestine, lung or liver. We show that the dose rate at which a lethal dose of total-body radiation is delivered does not augment hematopoietic progenitor stem cell homing to the bone marrow, spleen or sites of early radiation-mediated tissue damage at either 2 or 5 days postirradiation/transplantation. The observation that greater homing was seen in unirradiated control mice calls into question the concept that adequate bone marrow stem cell homing requires radiation-induced "space" to be made in the marrow.. certainly for the enriched early progenitor hematopoietic stem cells used for this set of experiments. Further experiments will be needed to determine whether these homed cells are as capable of giving rise to long-term engraftment/repopulation of the marrow of secondary recipients as they are in irradiated recipients. (C) 2004 by Radiation Research Society.