Localized donor cells in brain of a Hunter disease patient after cord blood stem cell transplantation
Localized donor cells in brain of a Hunter disease patient after cord blood stem cell transplantation
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DOI：
10.1016/j.ymgme.2009.05.006
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发表时间：
2009-11-01
影响因子：
3.8
通讯作者：
Ozono, Keiichi
中科院分区：
文献类型：
--
作者：
Araya, Ken;Sakai, Norio;Ozono, Keiichi
造血干细胞移植(HSCT)治疗Hunter病(艾杜酸-2-硫酸酯酶缺乏症)的疗效尚不清楚。我们用脐带血干细胞移植(CBSCT)治疗了一名患有严重亨特病的6岁男性：然而，他在治疗后10个月死于喉部移植后淋巴增生性疾病。在CBSCT后的随访期内，他的多动症、估计的精神年龄和脑MR结果没有改善。我们通过尸检组织的生化和病理分析来评估CBSCT的疗效。脑组织中有大量膨大的细胞，底物堆积，而肝脏中则没有。虽然肝脏中的IDS酶活性达到正常对照水平的40%左右，但大脑中的IDS酶活性仍然很低。然而，可变数量的串联重复序列分析表明，不仅在肝脏，而且在大脑中都有一条来自供体的微弱条带。此外，不仅在Kupffer细胞中，而且在肝细胞中也广泛地发现了在肝脏中的IDS免疫反应性。另一方面，患者脑组织中仅有CD68阳性的小胶质细胞/单核细胞表达，而正常脑组织中的神经元和少突胶质细胞也有表达。这些供体来源的入侵检测阳性细胞主要分布在血管周围间隙，其中一些明显存在于脑实质。在治疗10个月后，CBSCT的疗效被判断为对大脑不够有效。然而，对脑实质中供体来源的细胞的病理检测表明，HSCT在治疗Hunter病的神经症状方面具有潜力。这是第一份记录CBSCT后供体来源的细胞在大脑中分布到亨特病患者体内的神经病理学报告。(C)2009 Elsevier Inc.保留所有权利。
The efficacy of hematopoietic stem cell transplantation (HSCT) for Hunter disease (deficiency of iduronate-2-sulfatase, IDS) remains unclear. We treated a 6-year-old male suffering from a severe type of Hunter disease with cord blood stem cell transplantation (CBSCT): however, he died at 10 months post-therapy due to a laryngeal post-transplantation lymphoproliferative disorder. During the follow-up period after CBSCT, his hyperactivity, estimated mental age, and brain MR findings had not improved. We assessed the efficacy of CBSCT by biochemical and pathological analyses of the autopsied tissues. There were many distended cells with accumulated substrate in the brain, but not in the liver. IDS enzyme activity in the cerebrum remained very low, although that in the liver reached about 40% of the normal control level. However, a variable number of tandem repeats analyses demonstrated a weak donor-derived band not only in the liver but also in the cerebrum. Furthermore, IDS-immunoreactivity in the liver was recognized broadly not only in Kupffer cells but also in hepatocytes. On the other hand, IDS-immunoreactivity was recognized exclusively in CD68-positive microglia/monocytes in the patient's brain; whereas that in the normal brain was also detected in neurons and oligodendrocytes. These donor-derived IDS-positive cells were predominantly localized in perivascular spaces and some of them were evidently present in the brain parenchyma. The efficacy of CBSCT was judged to be insufficient for the brain at 10 months post-therapy. However, the pathological detection of donor-derived cells in the brain parenchyma suggests the potential of HSCT for treatment of neurological symptoms in Hunter disease. This is the first neuropathological report documenting the distribution of donor-derived cells in the brain after CBSCT into a Hunter disease patient. (C) 2009 Elsevier Inc. All rights reserved.