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) or Abcd1‐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.

中文翻译：

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骨髓移植到 Abcd1 缺陷小鼠：供体衍生细胞的分布和受体小鼠大脑的生物学特征

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超长链脂肪酸（VLCFA）在组织中的异常积累，尤其是大脑。目前，疾病早期的骨髓移植（BMT）是阻止疾病进展的唯一有效治疗方法，但治疗的潜在机制尚不清楚。在这里，我们将表达 GFP 的野生型 (WT) 或Abcd1 缺陷型(KO) 骨髓细胞移植到受体 KO 小鼠中，从而能够追踪供体 GFP ⁺受体小鼠的细胞。WT 和 KO 供体细胞在整个脑实质中均等分布，并显示 Iba1 阳性、GFAP 和 Olig2 阴性表型，表明大多数供体细胞被移植为小胶质细胞样细胞。它们约占 Iba1 阳性细胞的 40%。出乎意料的是，当将 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 患者大脑中的骨髓衍生的小胶质细胞样细胞可以抑制疾病进展，而不会明显减少大脑中 VLCFA 的含量。