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

Stem Cell Reports
Stephanie DoovesVivi M Heine

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.

Citations

Dec 13, 2019·Expert Review of Neurotherapeutics·Mahmoud Reza AshrafiAli Reza Tavasoli
Oct 14, 2020·Clinical Genetics·Anju ShuklaKatta Mohan Girisha
Jan 9, 2021·Seminars in Cell & Developmental Biology·Steven A GoldmanPernille M Madsen
May 13, 2021·ACS Applied Materials & Interfaces·Shreyas KuddannayaJeff W M Bulte
Jul 10, 2021·Frontiers in Cellular Neuroscience·Georg von JonquieresGary D Housley
Dec 9, 2021·Acta Neuropathologica·Marianna BugianiMarjo S van der Knaap

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Methods Mentioned

BETA
transgenic
genotyping

Software Mentioned

SPSS Statistics
SPSS
GLAST

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