Bone marrow transplantation into Abcd1‐deficient mice: Distribution of donor derived‐cells and biological characterization of the brain of the recipient mice
Bone marrow transplantation into Abcd1‐deficient mice: Distribution of donor derived‐cells and biological characterization of the brain of the recipient mice
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骨髓移植到 Abcd1 缺陷小鼠中：供体来源细胞的分布和受体小鼠大脑的生物学特征
DOI：
10.1002/jimd.12346
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发表时间：
2021
影响因子：
4.2
通讯作者：
Imanaka Tsuneo
中科院分区：
文献类型：
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作者：
Morita Masashi;Kaizawa Taro;Yoda Taiki;Oyama Takuro;Asakura Reina;Matsumoto Shun;Nagai Yoshinori;Watanabe Yasuharu;Watanabe Shiro;Kobayashi Hiroshi;Kawaguchi Kosuke;Yamamoto Seiji;Shimozawa Nobuyuki;So Takanori;Imanaka Tsuneo
X-连锁肾上腺脑白质营养不良（X-ALD）是一种严重的遗传性代谢疾病，伴有脑炎性脱髓鞘和组织（尤其是脑）中极长链脂肪酸（VLCFA）的异常蓄积。目前，在疾病的早期阶段进行骨髓移植（BMT）是阻止疾病进展的唯一有效治疗方法，但治疗的潜在机制仍不清楚。在这里，我们将表达GFP的野生型（WT）或Abcd 1缺陷型（KO）骨髓细胞移植到受体KO小鼠中，这使得能够在受体小鼠中追踪供体GFP+细胞。WT和KO供体细胞均均匀分布在整个脑实质中，并显示出Iba 1阳性、GFAP和Olig 2阴性表型，表明大多数供体细胞作为小胶质细胞样细胞移植。它们约占Iba 1阳性细胞的40%。出乎意料的是，当WT骨髓细胞移植到KO小鼠中时，没有观察到大脑中VLCFA的减少。总之，小鼠研究表明，移植到X-ALD患者大脑中的骨髓来源的小胶质细胞样细胞抑制了疾病进展，而没有明显减少大脑中VLCFA的量。
X‐linked adrenoleukodystrophy (X‐ALD) is a severe inherited metabolic disease with cerebral inflammatory demyelination and abnormal accumulation of very long chain fatty acid (VLCFA) in tissues, especially the brain. At present, bone marrow transplantation (BMT) at an early stage of the disease is the only effective treatment for halting disease progression, but the underlying mechanism of the treatment has remained unclear. Here, we transplanted GFP‐expressing wild‐type (WT) orAbcd1‐deficient (KO) bone marrow cells into recipient KO mice, which enabled tracking of the donor GFP+cells in the recipient mice. Both the WT and KO donor cells were equally distributed throughout the brain parenchyma, and displayed an Iba1‐positive, GFAP‐ and Olig2‐negative phenotype, indicating that most of the donor cells were engrafted as microglia‐like cells. They constituted approximately 40% of the Iba1‐positive cells. Unexpectedly, no decrease of VLCFA in the cerebrum was observed when WT bone marrow cells were transplanted into KO mice. Taken together, murine study suggests that bone marrow‐derived microglia‐like cells engrafted in the cerebrum of X‐ALD patients suppress disease progression without evidently reducing the amount of VLCFA in the cerebrum.