Goebel W Scott, Pech Nancy K, Dinauer Mary C
Herman B. Wells Center for Pediatric Research, James Whitcomb Riley Hospital for Children, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
Blood Cells Mol Dis. 2004 Nov-Dec;33(3):365-71. doi: 10.1016/j.bcmd.2004.06.007.
We previously demonstrated that low-dose radiation conditioning impairs murine hematopoietic stem cell function, permitting engraftment of syngeneic fresh and transduced marrow cells. In this study, we directly examined the ability of low-dose radiation conditioning to permit engraftment of transduced long-term repopulating cells in murine X-linked chronic granulomatous disease (X-CGD), which closely mimics the human disease. X-CGD mice conditioned with 160 cGy were transplanted with 20 x 10(6) MSCV-m91Neo-transduced syngeneic X-CGD marrow cells. The presence of oxidase-positive neutrophils in two independent cohorts of transplanted 160-cGy-conditioned X-CGD recipients was determined by nitroblue tetrazolium testing. Transplanted X-CGD mice (n = 9 total) displayed 1-17% oxidase-positive neutrophils 6-16 months post-transplant. Retroviral marking and NADPH-oxidase-positive neutrophils persisted through serial transplantation, verifying that stem cells were transduced. These results establish that low-dose radiation conditioning results in durable engraftment of low but potentially clinically relevant numbers of functionally reconstituted blood cells in a murine model of X-CGD.
我们之前证明，低剂量辐射预处理会损害小鼠造血干细胞功能，从而使同基因新鲜和转导的骨髓细胞得以植入。在本研究中，我们直接检测了低剂量辐射预处理在小鼠X连锁慢性肉芽肿病（X-CGD，其与人类疾病极为相似）中使转导的长期重建造血细胞得以植入的能力。用160 cGy进行预处理的X-CGD小鼠接受了20×10⁶个经MSCV-m91Neo转导的同基因X-CGD骨髓细胞的移植。通过硝基蓝四氮唑试验确定了两个独立队列中经160 cGy预处理的移植X-CGD受体中氧化酶阳性中性粒细胞的存在情况。移植后的X-CGD小鼠（共9只）在移植后6 - 16个月显示出1% - 17%的氧化酶阳性中性粒细胞。逆转录病毒标记和NADPH氧化酶阳性中性粒细胞在连续移植后持续存在，证实干细胞已被转导。这些结果表明，在X-CGD小鼠模型中，低剂量辐射预处理可导致低数量但可能具有临床相关性的功能重建血细胞持久植入。
