PROJECT: JTC2016: NEURONICHE

In mammals including humans, loss of function after spinal cord injury is permanent and injury repair is limited, characterised by reactive gliosis, fibrosis and scarring, despite the presence of spinal progenitor cells in a niche at the central canal. In contrast, these very similar niche cells in adult zebrafish spinal cord produce neurons after injury, and full locomotor function returns within 4-6 weeks after injury. Objectives: We hypothesize that small differences in the environment of zebrafish and mammalian spinal stem/progenitor cells determine regenerative success or failure. WP 1: We will promote spinal cord recovery by identifying and applying novel factors activating the neural niche to produce new neurons and promote myelination and by stimulating 5HT innervation (JPH, CGB, MMR, US) WP 2: We will control the fate of stem cells in vivo and ex vivo (MK, JPH, CGB, MMR) WP 3: We will develop tools to monitor the restorative events at the lesion site, to interfere with pathways hindering successful recovery and derive stem cell lines from the human central canal niche (SM, MK, JPH) Translatability is a cornerstone of this project. It will generate significant knowledge on the mechanisms of endogenous spinal cord repair, functionally tested in an in vivo spinal cord model, with direct human validation (through expression and in vitro studies of human material/cells). Furthermore, valuable tools will be created which will drive innovation and therapy development.