Axonal regeneration and myelination upon transplantation of genetically modifed adult neural stem cells

• Applicant: Professor Patrick Küry, Ph.D.
• Subject Area: Molecular and Cellular Neurology and Neuropathology
• Term: from 2015 to 2020
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 277317811

The generation of new oligodendrocytes and the repair of myelin sheaths represent processes that are essential for functional restoration after axonal injury. We identified the multifunctional p57kip2 protein as a negative regulator of myelinating glial cell differentiation and as an important intrinsic switch for glial fate decision in adult neural stem cells. In the proposed project, we will investigate to what extent transplantation of genetically modulated adult neural stem cells can induce myelination and axonal regeneration in the injured spinal cord and optic nerve. As previously shown, p57kip2-suppressed adult neural stem cells are slowly directed towards the oligodendroglial lineage concomitant with induction of bone morphogenetic protein (BMP) antagonist expression. On the one hand, we will examine to what degree the generation of new oligodendroglial cells can enhance myelination of regenerated axons. On the other and, as neural stem cell grafts are expected to generate an axonal growth permissive environment, we will also study the potential of these cells to stimulate axonal regeneration as such. We will perform first combinatorial approaches by co-transplanting unrestricted somatic stem cells (USSCs) and p57kip2-suppressed adult neural stem cells into lesioned spinal cords. Moreover, we will transplant p57kip2-suppressed adult neural stem cells into regenerating optic nerves upon inflammatory stimulation (IS). This will provide the unique opportunity to assess synergistic or complementary repair effects. Exchange within the Research Unit will also allow to analyze whether stem cell modulated central nervous system (CNS) regeneration affects the expression of further investigated factors such as neuronal MLP and ALCAM and to what degree genetically modified neural stem cells can confer immunomodulation

• DFG Programme: Research Grants