Cell Replacement Therapy Improves Pathological Hallmarks in a Mouse Model of Leukodystrophy Vanishing White Matter

Stephanie Dooves, Prisca S. Leferink, Sander Krabbenborg, Nicole Breeuwsma, Saskia Bots, Anne E.J. Hillen, Gerbren Jacobs, Marjo S. van der Knaap, Vivi M. Heine*

*Corresponding author for this work

Research output: Contribution to JournalArticleAcademicpeer-review


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 languageEnglish
Pages (from-to)441-450
Number of pages10
JournalStem cell reports
Issue number3
Early online date21 Feb 2019
Publication statusPublished - 5 Mar 2019


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.

FundersFunder number
IDB9003037601, 116005006
KNAW Ter Meulen Fonds
NWO Spinoza
ZonMw VIDI91712343
Nederlandse Organisatie voor Wetenschappelijk Onderzoek


    • astrocytes
    • cell replacement therapy
    • glial cells
    • leukodystrophy
    • oligodendrocytes
    • stem cells
    • vanishing white matter
    • white matter disorder


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