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 |
|---|---|
| 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 |
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Keywords
- astrocytes
- cell replacement therapy
- glial cells
- leukodystrophy
- oligodendrocytes
- stem cells
- vanishing white matter
- white matter disorder
Cite this
}
Cell Replacement Therapy Improves Pathological Hallmarks in a Mouse Model of Leukodystrophy Vanishing White Matter. / Dooves, Stephanie; Leferink, Prisca S.; Krabbenborg, Sander; Breeuwsma, Nicole; Bots, Saskia; Hillen, Anne E.J.; Jacobs, Gerbren; van der Knaap, Marjo S.; Heine, Vivi M.
In: Stem cell reports, Vol. 12, No. 3, 05.03.2019, p. 441-450.Research output: Contribution to Journal › Article › Academic › peer-review
TY - JOUR
T1 - Cell Replacement Therapy Improves Pathological Hallmarks in a Mouse Model of Leukodystrophy Vanishing White Matter
AU - Dooves, Stephanie
AU - Leferink, Prisca S.
AU - Krabbenborg, Sander
AU - Breeuwsma, Nicole
AU - Bots, Saskia
AU - Hillen, Anne E.J.
AU - Jacobs, Gerbren
AU - van der Knaap, Marjo S.
AU - Heine, Vivi M.
PY - 2019/3/5
Y1 - 2019/3/5
N2 - 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.
AB - 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.
KW - astrocytes
KW - cell replacement therapy
KW - glial cells
KW - leukodystrophy
KW - oligodendrocytes
KW - stem cells
KW - vanishing white matter
KW - white matter disorder
UR - http://www.scopus.com/inward/record.url?scp=85062066332&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85062066332&partnerID=8YFLogxK
U2 - 10.1016/j.stemcr.2019.01.018
DO - 10.1016/j.stemcr.2019.01.018
M3 - Article
VL - 12
SP - 441
EP - 450
JO - Stem cell reports
JF - Stem cell reports
SN - 2213-6711
IS - 3
ER -