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Successful Treatment of Metachromatic Leukodystrophy Using Bone Marrow Transplantation of HoxB4 Overexpressing Cells

Miyake, Noriko; Miyake, Koichi; Karlsson, Stefan LU and Shimada, Takashi (2010) In Molecular Therapy 18(7). p.1373-1378
Abstract
To evaluate the contribution of bone marrow (BM) cells to treat neurological disorders, we examined the effectiveness of BM cells expressing the homeobox B4 (HoxB4) gene to cure mice with metachromatic leukodystrophy (MLD) through transplantation. Increased number of donor cells was observed in brains of the MLD mice transplanted with HoxB4-transduced BM cells (B4MLD) in contrast to those transplanted with control green fluorescent protein (GFP)-transduced BM cells (MIGMLD). Immunohistochemical staining showed that most of the GFP(+) cells were Iba1(+) microglia. In addition, O4(+) oligodendrocytes were identified only in the B4MLD brains but not in the MIGMLD brain. Alcian blue staining showed that accumulation of sulfatide was... (More)
To evaluate the contribution of bone marrow (BM) cells to treat neurological disorders, we examined the effectiveness of BM cells expressing the homeobox B4 (HoxB4) gene to cure mice with metachromatic leukodystrophy (MLD) through transplantation. Increased number of donor cells was observed in brains of the MLD mice transplanted with HoxB4-transduced BM cells (B4MLD) in contrast to those transplanted with control green fluorescent protein (GFP)-transduced BM cells (MIGMLD). Immunohistochemical staining showed that most of the GFP(+) cells were Iba1(+) microglia. In addition, O4(+) oligodendrocytes were identified only in the B4MLD brains but not in the MIGMLD brain. Alcian blue staining showed that accumulation of sulfatide was dramatically reduced in brain tissue from B4MLD mice, and there was a corresponding improvement in the animals' ability to walk a balance beam 8 months after transplantation. Thus transplantation of BM cells overexpressing HoxB4 appears to effectively prevent the progression of MLD in this mouse model. These findings support the idea that hematopoietic stem cells (HSCs) transduced with a HoxB4 expression vector could be the useful carriers of therapeutic proteins into the brain for regeneration of oligodendrocytes to treat such demyelinating disorders as MLD, Krabbe disease, and multiple sclerosis. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Molecular Therapy
volume
18
issue
7
pages
1373 - 1378
publisher
Nature Publishing Group
external identifiers
  • wos:000279398900016
  • scopus:77954242057
ISSN
1525-0024
DOI
10.1038/mt.2010.74
language
English
LU publication?
yes
id
2e76335d-4ba5-49c6-bd96-f22b26157a22 (old id 1628967)
date added to LUP
2010-07-23 11:16:54
date last changed
2018-05-29 10:19:06
@article{2e76335d-4ba5-49c6-bd96-f22b26157a22,
  abstract     = {To evaluate the contribution of bone marrow (BM) cells to treat neurological disorders, we examined the effectiveness of BM cells expressing the homeobox B4 (HoxB4) gene to cure mice with metachromatic leukodystrophy (MLD) through transplantation. Increased number of donor cells was observed in brains of the MLD mice transplanted with HoxB4-transduced BM cells (B4MLD) in contrast to those transplanted with control green fluorescent protein (GFP)-transduced BM cells (MIGMLD). Immunohistochemical staining showed that most of the GFP(+) cells were Iba1(+) microglia. In addition, O4(+) oligodendrocytes were identified only in the B4MLD brains but not in the MIGMLD brain. Alcian blue staining showed that accumulation of sulfatide was dramatically reduced in brain tissue from B4MLD mice, and there was a corresponding improvement in the animals' ability to walk a balance beam 8 months after transplantation. Thus transplantation of BM cells overexpressing HoxB4 appears to effectively prevent the progression of MLD in this mouse model. These findings support the idea that hematopoietic stem cells (HSCs) transduced with a HoxB4 expression vector could be the useful carriers of therapeutic proteins into the brain for regeneration of oligodendrocytes to treat such demyelinating disorders as MLD, Krabbe disease, and multiple sclerosis.},
  author       = {Miyake, Noriko and Miyake, Koichi and Karlsson, Stefan and Shimada, Takashi},
  issn         = {1525-0024},
  language     = {eng},
  number       = {7},
  pages        = {1373--1378},
  publisher    = {Nature Publishing Group},
  series       = {Molecular Therapy},
  title        = {Successful Treatment of Metachromatic Leukodystrophy Using Bone Marrow Transplantation of HoxB4 Overexpressing Cells},
  url          = {http://dx.doi.org/10.1038/mt.2010.74},
  volume       = {18},
  year         = {2010},
}