Goebel W Scott, Dinauer Mary C
Department of Pediatrics (Hematology/Oncology), Indiana University School of Medicine, 1044 W. Walnut Street, Indianapolis, IN 46202, USA.
J Pediatr Hematol Oncol. 2002 Dec;24(9):787-90. doi: 10.1097/00043426-200212000-00026.
Our laboratory has reported the correction of neutrophil NADPH oxidase function by retroviral-mediated gene transfer (RMGT) in murine X-linked chronic granulomatous disease (X-CGD). Few studies, however, have used nonmyeloablative conditioning in conjunction with RMGT. Promising methods of decreased intensity conditioning include low dose irradiation and antimetabolite conditioning. Preliminary studies using syngeneic mice transplanted with fresh marrow cells indicate that high levels of donor cell chimerism can be achieved with low-dose radiation or 5-fluorouracil-based conditioning regimens. Early data from experiments in which low-dose radiation-conditioned X-CGD recipients were transplanted with retrovirus-transduced X-CGD marrow cells show that gene-corrected neutrophils can be detected by NBT assay for NADPH oxidase activity reconstitution 4 months posttransplant, although these levels are much lower than the 50%-70% gene-corrected cell detected in lethally irradiated recipients. Transplantation of retrovirus-transduced marrow cells into 5-fluorouracil conditioned hosts is also being explored.
我们实验室报道了通过逆转录病毒介导的基因转移（RMGT）纠正小鼠X连锁慢性肉芽肿病（X-CGD）中性粒细胞NADPH氧化酶功能。然而，很少有研究将非清髓性预处理与RMGT联合使用。降低强度预处理的有前景的方法包括低剂量照射和抗代谢物预处理。使用同基因小鼠移植新鲜骨髓细胞的初步研究表明，低剂量辐射或基于5-氟尿嘧啶的预处理方案可实现高水平的供体细胞嵌合。在低剂量辐射预处理的X-CGD受体移植逆转录病毒转导的X-CGD骨髓细胞的实验中，早期数据显示，移植后4个月通过NBT试验检测NADPH氧化酶活性重建可检测到基因校正的中性粒细胞，尽管这些水平远低于在接受致死性照射的受体中检测到的50%-70%的基因校正细胞。将逆转录病毒转导的骨髓细胞移植到5-氟尿嘧啶预处理的宿主中也在探索中。
