Therapeutic effects of normal cells on ABCD1 deficient cells in vitro and hematopoietic cell transplantation in the X-ALD mouse model

Takeshi Yamada, Yasumasa Ohyagi, Nobue Shinnoh, Hitoshi Kikuchi, Manabu Osoegawa, Hirofumi Ochi, Jun Ichi Kira, Hirokazu Furuya

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

Bone marrow transplantation (BMT) is accepted as an efficient therapy for X-linked adrenoleukodystrophy (ALD). To clarify the mechanisms of this treatment, we examined the effects of hematopoietic cell transplantation (HCT) in an ATP-binding cassette, subfamily D, member 1 (ABCD1) knock out mice and co-culture of ALD patient fibroblasts with normal cells. We treated ABCD1 knock out mice with HCT using lacZ-transgenic mice as donors, which enabled us to detect donor-derived cells. We also examined the effects of co-culturing a normal microglia cell line (N9) with ALD fibroblasts. β-Galactosidase (β-GAL) activity was higher in spleen, lung and kidney than in liver, brain and spinal cord of the recipient ABCD1 knock out mice. HCT reduced the accumulation of very long chain fatty acid (VLCFA) in those tissues. The reduction of the VLCFA ratio was significant in spleen and lung; tissues with higher β-GAL activity. ABCD1 was detectable in spleen from HCT mice. Co-culture of ALD fibroblasts with normal fibroblast cells reduced VLCFA accumulation in ALD cells. This effect was not observed when the cells were co-cultured while separated by a filter membrane. Our data suggest that supplying normal cells for ABCD1 knockout mouse by HCT corrects metabolic abnormalities in ALD tissues through a cell-mediated process. The correction requires direct cell-to-cell contact for recovering normal cell function.

Original languageEnglish
Pages (from-to)91-97
Number of pages7
JournalJournal of the Neurological Sciences
Volume218
Issue number1-2
DOIs
Publication statusPublished - Mar 15 2004

All Science Journal Classification (ASJC) codes

  • Neurology
  • Clinical Neurology

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