| Krabbe's disease is a degenerative neurological disorder with rapidly progressive demyelination of the central and peripheral nervous systems. It is a lysosomal storage disease that results from an autosomal recessive mutation in the galactocerebrosidase (GALC) gene, which severely affects the activity of the enzyme. To date, the only treatment option available for Krabbe's patients is hematopoietic cell transplantation, which has only limited success, must be administered before the development of any symptoms, and is often complicated by graft-versus-host-disease.;Mesenchymal stem cells (MSCs) and neural stem cells (NSCs) are self-renewing multipotent cells that generate the main phenotypes of their developmental lineage. These cells have the ability to affect the microenvironment of the distressed tissue through the secretion of trophic factors and anti-inflammatory effects. There is also a possibility for the delivery of enzymes and differentiation into the cell types that are already damaged by the disease.;NSCs and two types of MSCs from enhanced green fluorescent protein (eGFP) transgenic mice were transplanted into the lateral ventricles of 3--4 days old twitcher mice, the murine model of Krabbe's disease. The transplanted cells could be traced to various parts of the brain until 16--20 days post injection. The mice treated with these cells displayed an increase in lifespan, body weight, and motor function. The level of neuroinflammation was also reduced through a down-regulation of pro-inflammatory cytokines and chemokines, iNOS, macrophage infiltration and microglial activation. Additionally, the NSCs increased the GALC levels in the brain and were able to differentiate to a limited extent. However, this was not accompanied with increased myelin levels.;Overall, the MSCs and NSCs led to promising improvements in the twitcher mice with individual differences between the three cell groups. In spite of this progress, the mice still deteriorated and died with symptoms indistinguishable from untreated controls. |
