Jonas Frisén, Karolinska Institute, Stockholm, Sweden

Directing the fate of endogenous neural stem cell progeny to facilitate functional recovery after spinal cord injury

Funded in: 2018, 2019, 2020


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Problem: Disruption of myelin sheets enwrapping axons is known to cause axonal dysfunction and eventually death of the neuron

Target: Promotion of endogenous remyelination

Goal: Modify the generation of progeny by the stem cells to generate more myelinating oligodendrocytes

 

Spinal cord injury often leads to permanent functional deficits, caused by disruption of neuronal connections. Some nerve fibers are cut by the injury, and fail to reconnect with their target. Other axons may remain connected within their neural circuits, but may have lost myelination, i.e. the coat of fatty material that insulates axons. Disruption of myelin sheets enwrapping axons is known to cause axonal dysfunction and eventually death of the neuron. Supporting restoration of myelin is therefore recognized as a possible avenue to promote recovery after spinal cord injury.

There are neural stem cells in the adult spinal cord. These cells are activated after spinal cord injury, when they generate scar forming cells, a process that is important for restricting the injury and reinforcing the tissue to avoid further expansion of the lesion. The spinal cord stem cells can also generate oligodendrocytes, the cells that produce myelin. However, they generate an insufficient number of new oligodendrocytes.

In the current project, we will assess whether the generation of oligodendrocytes from spinal cord stem cells can be experimentally increased, and whether this promotes functional recovery. We have engineered genetically modified mice, in which we can steer the generation of progeny by the stem cells, so that they generate many more oligodendrocytes. We will study the regulation of how oligodendrocyte generation is regulated with the ultimate goal to contribute to therapies where neural function is improved after spinal cord injury.