AMD3100 redosing fails to repeatedly mobilize hematopoietic stem cells in the nonhuman primate and humanized mouse.
AMD3100 redosing fails to repeatedly mobilize hematopoietic stem cells in the nonhuman primate and humanized mouse.
复制标题
DOI：
10.1016/j.exphem.2020.11.001
复制
发表时间：
2021-01
影响因子：
2.6
通讯作者：
Humbert O
中科院分区：
文献类型：
--
作者：
Samuelson C;Radtke S;Cui M;Perez A;Kiem HP;Humbert O
AMD3100（普乐沙福）是许多临床和临床前移植方案的重要组成部分，通过动员进入外周血循环促进造血干细胞和祖细胞的采集。对于许多首次干细胞采集不佳或需要重复移植的患者，也需要使用AMD 3100进行重复动员。在本研究中，我们研究了在非人灵长类动物和人源化小鼠模型中重复给予AMD 3100的动员效力。在非人灵长类动物中，我们证明了首次给予AMD 3100后的有效动员，但后续剂量的药物在CD34+和富含造血干细胞的CD90+细胞中的应答显著较差。在植入人CD 34+细胞的免疫缺陷小鼠中发现了类似的重复给药疗效损失，与首次给药相比，第二次给药后总人白色细胞群，特别是人造血干细胞和祖细胞的动员效果显著降低。总之，我们的研究结果预计将告知未来的动员方案的目的，外周血造血干细胞提取或应用程序中，造血干细胞必须在体内传递的基因靶向剂。
AMD3100 (plerixafor) is a vital component of many clinical and pre-clinical transplant protocols, facilitating harvest of hematopoietic stem and progenitor cells through mobilization into the peripheral blood circulation. Repeat mobilization with AMD3100 is also necessary for many patients with suboptimal first stem cell collection or those requiring repeat transplantation. In this study we investigated the mobilization efficacy of repeated AMD3100 dosages in the non-human primate and humanized mouse models. In non-human primates we demonstrate effective mobilization after the first AMD3100 administration but significantly poorer response in CD34+ and hematopoietic stem cell-enriched CD90+ cells with subsequent doses of the drug. A similar loss of efficacy with repeated administration was found in immunodeficient mice engrafted with human CD34+ cells, in whom the total human white cell population and particularly human hematopoietic stem and progenitor cells mobilized significantly less effectively following a second AMD3100 administration when compared to first dose. Together, our results are expected to inform future mobilization protocols for the purposes of peripheral blood hematopoietic stem cell extraction or for applications in which hematopoietic stem cells must be made accessible for in vivo-delivered gene targeting agents.
登录
查看更多内容
影响因子：
20.3
作者：
Kean, Leslie S.;Sen, Sharon;Donahue, Robert E.
通讯作者：
Donahue, Robert E.
影响因子：
4.5
作者：
Fitzhugh, Courtney D.;Hsieh, Matthew M.;Tisdale, John F.
通讯作者：
Tisdale, John F.
DOI：
10.1016/j.omtm.2017.05.004
发表时间：
2017-09-01
影响因子：
4.7
作者：
Haworth, Kevin G.;Ironside, Christina;Kiem, Hans-Peter
通讯作者：
Kiem, Hans-Peter
影响因子：
16.6
作者：
Bahal, Raman;McNeer, Nicole Ali;Quijano, Elias;Liu, Yanfeng;Sulkowski, Parker;Turchick, Audrey;Lu, Yi-Chien;Bhunia, Dinesh C.;Manna, Arunava;Greiner, Dale L.;Brehm, Michael A.;Cheng, Christopher J.;Lopez-Giraldez, Francesc;Ricciardi, Adele;Beloor, Jagadish;Krause, Diane S.;Kumar, Priti;Gallagher, Patrick G.;Braddock, Demetrios T.;Saltzman, W. Mark;Ly, Danith H.;Glazer, Peter M.
通讯作者：
Glazer, Peter M.
影响因子：
20.3
作者：
Larochelle, A;Krouse, A;Hematti, P
通讯作者：
Hematti, P