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

Research output: Contribution to JournalArticleAcademicpeer-review

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 languageEnglish
Pages (from-to)441-450
Number of pages10
JournalStem cell reports
Volume12
Issue number3
Early online date21 Feb 2019
DOIs
Publication statusPublished - 5 Mar 2019

Fingerprint

Leukoencephalopathies
Cell- and Tissue-Based Therapy
Neuroglia
Stem Cells
Stem cells
Brain
Cell Transplantation
Myelin Sheath
Astrocytes
Rodentia
Defects
Therapeutics
White Matter
Population

Keywords

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

Cite this

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. / Cell Replacement Therapy Improves Pathological Hallmarks in a Mouse Model of Leukodystrophy Vanishing White Matter. In: Stem cell reports. 2019 ; Vol. 12, No. 3. pp. 441-450.
@article{da7fb917e18340e19213aecb0006bc1c,
title = "Cell Replacement Therapy Improves Pathological Hallmarks in a Mouse Model of Leukodystrophy Vanishing White Matter",
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.",
keywords = "astrocytes, cell replacement therapy, glial cells, leukodystrophy, oligodendrocytes, stem cells, vanishing white matter, white matter disorder",
author = "Stephanie Dooves and Leferink, {Prisca S.} and Sander Krabbenborg and Nicole Breeuwsma and Saskia Bots and Hillen, {Anne E.J.} and Gerbren Jacobs and {van der Knaap}, {Marjo S.} and Heine, {Vivi M.}",
year = "2019",
month = "3",
day = "5",
doi = "10.1016/j.stemcr.2019.01.018",
language = "English",
volume = "12",
pages = "441--450",
journal = "Stem cell reports",
issn = "2213-6711",
publisher = "Cell Press",
number = "3",

}

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 JournalArticleAcademicpeer-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 -