Defective Self-Renewal and Differentiation of GBA-Deficient Neural Stem Cells Can Be Restored By Macrophage Colony-Stimulating Factor.
Gaucher disease (GD) is an autosomal recessive lysosomal storage disorder caused by mutations in the glucocerebrosidase gene (GBA), which encodes the lysosomal enzyme glucosylceramidase (GCase). Deficiency in GCase leads to characteristic visceral pathology and lethal neurological manifestations in some patients. Investigations into neurogenesis have suggested that neurodegenerative disorders, such as GD, could be overcome or at least ameliorated by the generation of new neurons. Bone marrow-derived mesenchymal stem cells (BM-MSCs) are potential candidates for use in the treatment of neurodegenerative disorders because of their ability to promote neurogenesis. Our objective was to examine the mechanism of neurogenesis by BM-MSCs in GD. We found that neural stem cells (NSCs) derived from a neuronopathic GD model exhibited decreased ability for self-renewal and neuronal differentiation. Co-culture of GBA-deficient NSCs with BM-MSCs resulted in an enhanced capacity for self-renewal, and an increased ability for differentiation into neurons or oligodendrocytes. Enhanced proliferation and neuronal differentiation of GBA-deficient NSCs was associated with elevated release of macrophage colony-stimulating factor (M-CSF) from BM-MSCs. Our findings suggest that soluble M-CSF derived from BM-MSCs can modulate GBA-deficient NSCs, resulting in their improved proliferation and neuronal differentiation.
Stem Cell Neuroplasticity Research Group, Cell and Matrix Research Institute, College of Veterinary Medicine, Kyungpook National University, Daegu 702-701, Korea.|Department of Laboratory Animal Medicine, Cell and Matrix Research Institute, College of Veterinary Medicine, Kyungpook National University, Daegu 702-701, Korea.
Hyun
H
Lee
Stem Cell Neuroplasticity Research Group, Cell and Matrix Research Institute, College of Veterinary Medicine, Kyungpook National University, Daegu 702-701, Korea.|Department of Physiology, Cell and Matrix Research Institute, School of Medicine, Kyungpook National University, Daegu 700-842, Korea.|Department of Biomedical Science, BK21 Plus KNU Biomedical Convergence Program, Kyungpook National University, Daegu 700-842, Korea.
Jae-sung
JS
Bae
Stem Cell Neuroplasticity Research Group, Cell and Matrix Research Institute, College of Veterinary Medicine, Kyungpook National University, Daegu 702-701, Korea.|Department of Laboratory Animal Medicine, Cell and Matrix Research Institute, College of Veterinary Medicine, Kyungpook National University, Daegu 702-701, Korea.
Hee Kyung
HK
Jin
D000818:Animals; D002454:Cell Differentiation; D000066673:Cell Self Renewal; D002478:Cells, Cultured; D018920:Coculture Techniques; D004353:Drug Evaluation, Preclinical; D005776:Gaucher Disease / Q000188:drug therapy; D005962:Glucosylceramidase; D005963:Glucosylceramides / Q000378:metabolism; D016173:Macrophage Colony-Stimulating Factor / Q000494:pharmacology* / Q000502:physiology; D059630:Mesenchymal Stem Cells / Q000502:physiology; D008822:Mice, Transgenic; D009414:Nerve Growth Factors / Q000378:metabolism; D058953:Neural Stem Cells / Q000502:physiology*; D019899:Paracrine Communication
D005963:Glucosylceramides; D009414:Nerve Growth Factors; D016173:Macrophage Colony-Stimulating Factor; D005962:Glucosylceramidase
BM-MSC; M-CSF; gaucher disease; neural stem cells; neurogenesis