Abstract
Stem cell therapy has great prospects for brain white matter disorders, including the genetically determined disorders called leukodystrophies. We focus on the devastating leukodystrophy vanishing white matter (VWM). Patients with VWM show severe disability and early death, and treatment options are lacking. Previous studies showed successful cell replacement therapy in rodent models for myelin defects. However, proof-of-concept studies of allogeneic cell replacement in models representative of human leukodystrophies are lacking. We tested cell replacement in a mouse model representative of VWM. We transplanted different murine glial progenitor cell populations and showed improved pathological hallmarks and motor function. Improved mice showed a higher percentage of transplanted cells that differentiated into GFAP + astrocytes, suggesting best therapeutic prospects for replacement of astroglial lineage cells. This is a proof-of-concept study for cell transplantation in VWM and suggests that glial cell replacement therapy is a promising therapeutic strategy for leukodystrophy patients.
Original language | English |
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Pages (from-to) | 441-450 |
Number of pages | 10 |
Journal | Stem cell reports |
Volume | 12 |
Issue number | 3 |
Early online date | 21 Feb 2019 |
DOIs | |
Publication status | Published - 5 Mar 2019 |
Funding
This study was financially supported by the NWO Spinoza grant (M.S.v.d.K.), ZonMw VIDI research grant 91712343 (V.M.H.), the ZonMw TAS IDB project 116005006 (V.M.H.), E-Rare Joint Call project 9003037601 (V.M.H., M.S.v.d.K.), and KNAW Ter Meulen Fonds (S.D.). We thank Paulien Cornelissen for technical assistance.
Funders | Funder number |
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IDB | 9003037601, 116005006 |
KNAW Ter Meulen Fonds | |
NWO Spinoza | |
ZonMw TAS | |
ZonMw VIDI | 91712343 |
Nederlandse Organisatie voor Wetenschappelijk Onderzoek |
Keywords
- astrocytes
- cell replacement therapy
- glial cells
- leukodystrophy
- oligodendrocytes
- stem cells
- vanishing white matter
- white matter disorder