Research
Human Disease Models and Stem Cell Therapy for Stroke
I. Human Disease Models
Over the pass few years, we have taken advantage of both the SMA and ADPKD mouse models we established to elucidate pathogenic mechanisms and design therapeutic protocols.
The pathogenesis of spinal muscular atrophy
The molecular pathomechanism of SMA is not yet understood. Spinal motor neurons from SMA mice showed a distinct gene expression profile from the control mice. Downregulated genes included those associated with cytoskeleton/axonal transport and cell surface antigens/receptors, such as dynactin and microtubuleassociated proteins. In contrast, cell death-associated genes were mostly upregulated. The motor neuron-specific gene expression profile from the SMA mouse model should provide direct information on the genes leading to neurodegeneration and neuronal death and should be useful for developing new therapeutic strategies.
II. Stem Cell Therapy for Stroke
Stroke is a leading cause of death and disability worldwide; with no effective therapy currently available. The expression of CXC chemokine receptor 4 (CXCR4) and stromal cell-derived factor 1£\ (SDF-1£\) following focal cerebral ischemia led us to speculate that this chemokine may also signal adhesion and migration of HSCs to ischemic tissue. SDF-1£\ plays a role not only in stem cell differentiation but also in ischemia-induced trafficking of stem cells from peripheral blood to the damaged brain. If a sufficient number of HSCs could home in on cerebral ischemic injuries to promote neuronal repair and recovery of function, this would provide a novel insight into the mechanisms driving stem cell differentiation and recruitment into damaged tissues.
