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. 2021 May;44(3):718-727.
doi: 10.1002/jimd.12346. Epub 2021 Jan 4.

Bone marrow transplantation into Abcd1-deficient mice: Distribution of donor derived-cells and biological characterization of the brain of the recipient mice

Masashi Morita  1 , Taro Kaizawa  1 , Taiki Yoda  1 , Takuro Oyama  1 , Reina Asakura  1 , Shun Matsumoto  1 , Yoshinori Nagai  2 , Yasuharu Watanabe  3 , Shiro Watanabe  4 , Hiroshi Kobayashi  5 , Kosuke Kawaguchi  1 , Seiji Yamamoto  6 , Nobuyuki Shimozawa  7 , Takanori So  1 , Tsuneo Imanaka  8
Affiliations

Bone marrow transplantation into Abcd1-deficient mice: Distribution of donor derived-cells and biological characterization of the brain of the recipient mice

Masashi Morita et al. J Inherit Metab Dis. 2021 May.

Abstract

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.

Keywords: ABCD1; X-linked adrenoleukodystrophy; bone marrow transplantation; green fluorescence protein; peroxisome; very long chain fatty acid.

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References

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