Accelerated lymphocyte reconstitution and long-term recovery after transplantation of lentiviral-transduced rhesus CD34+ cells mobilized by G-CSF and plerixafor
Accelerated lymphocyte reconstitution and long-term recovery after transplantation of lentiviral-transduced rhesus CD34+ cells mobilized by G-CSF and plerixafor
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DOI：
10.1016/j.exphem.2011.04.002
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发表时间：
2011-07-01
影响因子：
2.6
通讯作者：
Donahue, Robert E.
中科院分区：
文献类型：
--
作者：
Uchida, Naoya;Bonifacino, Aylin;Donahue, Robert E.
Objective.粒细胞集落刺激因子（G-CSF）联合普乐沙福可显著动员恒河猴中的CD 34（+）细胞。我们试图评估这些CD 34（+）细胞是否可以稳定地重建慢病毒基因标记的血细胞。我们使用慢病毒载体转导的G-CSF和普乐沙福动员的恒河猴CD 34（+）细胞进行造血干细胞移植，并将这些数据与G-CSF和干细胞因子动员的数据进行比较。G-CSF和plerixafor动员导致的CD 34（+）细胞产量是G-CSF和干细胞因子的两倍。与单独使用G-CSF相比，G-CSF和普乐沙福动员的CD 34（+）细胞中的CD 123（白细胞介素-3受体）表达更高。移植G-CSF和普乐沙福动员细胞的动物显示所有谱系的植入，与接受G-CSF和干细胞因子动员移植物的动物相似。在接受G-CSF和普乐沙福动员的CD 34（+）细胞的动物中，淋巴细胞植入加速。在淋巴细胞快速恢复的前3个月期间，G-CSF和普乐沙福组的1只动物出现冷凝集素相关皮疹。移植后一年，所有动物的所有血细胞系中有2%至10%的转基因表达。G-CSF和普乐沙福动员的CD 34（+）细胞加速淋巴细胞植入，并含有能够重建多系血细胞的造血干细胞。这些结果表明，在恒河猴中基于普乐沙福的造血干细胞动员方案中需要考虑的重要差异。(C)2011 ISEH -血液学和干细胞学会。爱思唯尔公司出版
Objective. Granulocyte colony-stimulating factor (G-CSF) in combination with plerixafor produces significant mobilization of CD34(+) cells in rhesus macaques. We sought to evaluate whether these CD34(+) cells can stably reconstitute blood cells with lentiviral gene marking.Materials and Methods. We performed hematopoietic stem cell transplantation using G-CSF and plerixafor-mobilized rhesus CD34(+) cells transduced with a lentiviral vector, and these data were compared with those of G-CSF and stem cell factor mobilization.Results. G-CSF and plerixafor mobilization resulted in CD34(+) cell yields that were twofold higher than yields with G-CSF and stem cell factor. CD123 (interleukin-3 receptor) expression was greater in G-CSF and plerixafor-mobilized CD34(+) cells when compared to G-CSF alone. Animals transplanted with G-CSF and plerixafor-mobilized cells showed engraftment of all lineages, similar to animals who received G-CSF and stem cell factor mobilized grafts. Lymphocyte engraftment was accelerated in animals receiving the G-CSF and plerixaformobilized CD34(+) cells. One animal in the G-CSF and plerixafor group developed cold agglutinin-associated skin rash during the first 3 months of rapid lymphocyte recovery. One year after transplantation, all animals had 2% to 10% transgene expression in all blood cell lineages.Conclusions. G-CSF and plerixafor-mobilized CD34(+) cells accelerate lymphocyte engraftment and contain hematopoietic stein cell capable of reconstituting multilineage blood cells. These findings indicate important differences to consider in plerixafor-based hematopoietic stem cell mobilization protocols in rhesus macaques. (C) 2011 ISEH - Society for Hematology and Stem Cells. Published by Elsevier Inc.