Jonas Frisén / Enric Llorens-Bobadilla, Karolinska Institute, Department of Cell and Molecular Biology, Stockholm, Sweden

Nudging resident stem cells to make new neurons

Funded in: 2022, 2023, 2024

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Problem: Resident neural stem cells form scar tissue but are not involved in regeneration
Target: Convince resident neural stem cells to start making neurons
Goal: Promote the self-repair potential of the spinal cord

The mammalian spinal cord contains some neural stem cells, yet it does not regenerate very efficiently. Part of the problem is that these neural stem cells, instead of making the cell types needed for regeneration, such as neurons, form scar tissue. When transplanted into the injured spinal cord, stem cells can make new neurons that connect to surviving axons and bridge the lesion site. But, to avoid the need for transplantation, could human beings convince resident neural stem cells to start making neurons?

All the neurons in the nervous system are generated during development by following a set of instructions from our genome. There are many types of neurons, each having a different function. Thanks to recent technological advances, the neuroscientists can now differ exactly which instructions need to be read to create specific neuron types. In this project, the researchers aim to use this knowledge to force neural stem cells in the adult spinal cord to read the sets of instructions to make new neurons after damage. They will achieve this by using new genetic tools that allow them to control which genes are active in specific cells with high precision. Testing many genes at the same time aims at sorting out those with the strongest capacity to force neuron generation from stem cells. Once they find the best ones, they will activate these genes in models of spinal cord injury. The scientists will use therapies that would mimic the situation in the clinic as much as possible. Their hope is that this study opens the door to testing new treatment strategies aimed at promoting the self-repair potential of the spinal cord.