Mobilization as a preparative regimen for hematopoietic stem cell transplantation
Mobilization as a preparative regimen for hematopoietic stem cell transplantation
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DOI：
10.1182/blood-2005-09-3593
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发表时间：
2006-05-01
期刊：
影响因子：
20.3
通讯作者：
Abkowitz, JL
中科院分区：
文献类型：
--
作者：
Chen, J;Larochelle, A;Abkowitz, JL
目前造血干细胞（HSC）移植的清髓预处理方案与显着的发病率和死亡率相关。因此，需要通过增加安全性调查来促进输注的 HSC 植入的替代策略。使用联体小鼠，我们确定，在用 AMD3100（一种 CXCR4 拮抗剂）动员后，HSC 会从骨髓中排出，转运到血液中，并移植到伴侣骨髓的开放壁龛中。然后我们假设移植前的动员可能会腾出生态位并改善 HSC 植入。当 PeP3(b) 小鼠在移植 4 x 10(7) 骨髓细胞前 2 小时用 AMD3100 治疗时，供体细胞植入率高于对照动物 (4.6% +/- 1.1%)（无 AMD3100；1.0% +/- 0.24%，P < .001）。当小鼠连续 3 周每周注射 AMD3100 并在每次动员后 2 小时移植骨髓细胞时，供体细胞植入进一步增加 (9.1% +/- 1.7%, P = .001)。相比之下，在动员能力较差的 Balb/cByJ 小鼠的类似实验中，AMD3100 治疗组和对照受体的供体细胞植入之间没有差异。这些结果表明可用生态位的数量调节 HSC 的数量。此外，AMD3100 动员可以为遗传性疾病和其他非恶性疾病的 HSC 移植提供更安全的准备方法。
Current myeloablative conditioning regimens for hematopoietic stem cell (HSC) transplantation are associated with significant morbidity and mortality. Thus, alternative strategies to promote engraftment of infused HSCs with increased safety warrant investigation. Using parabiotic mice, we determined that, after mobilization with AMD3100 (a CXCR4 antagonist), HSCs exited from marrow, transited blood, and engrafted in open niches in partner marrow. We then hypothesized that mobilization before transplantation might vacate niches and improve HSC engraftment. When PeP3(b) mice were treated with AMD3100 at 2 hours before the transplantation of 4 x 10(7) marrow cells, donor cell engraftment was higher (4.6% +/- 1.1%) than in control animals (no AMD3100; 1.0% +/- 0.24%, P < .001). When mice received weekly injections of AMD3100 on 3 consecutive weeks and marrow cells were transplanted 2 hours after each mobilization, donor cell engraftment further increased (9.1% +/- 1.7%, P = .001). In contrast, in similar experiments with Balb/cByJ mice that mobilize poorly, there was no difference between the donor cell engraftment of AMD3100-treated and control recipients. These results indicate that the number of available niches regulates the number of HSCs. In addition, mobilization with AMD3100 may provide a safer preparative approach for HSC transplantation in genetic and other nonmalignant disorders.