12:00 – 12:30 Mª del Mar Sánchez Martín 

Optogenetic stimulation of stem cell grafts for the treatment of spinal cord injuries

Spinal Cord Injury (SCI) disrupts the communication between the brain and the spinal circuits responsible for a variety of neurological functions and coordinated movement, leading to motor, sensory and autonomic dysfunctions. Neural progenitor cells (NPC) emerge as one of the most promising treatments for SCI due to its multifaceted capabilities in replacing host cells (Kadoya et al., 2016), providing trophic support, modulating neuroinflammation, bridging lesions, thereby reinstating neuronal circuitry and connectivity. However, several challenges remain, such as improving graft survival, directing NPC differentiation towards desires neuronal lineages and establishing functional synaptic connections (Fischer et al., 2020).

Optogenetics has been extensively used for elucidating circuit dynamics and graft-host connectivity (Ceto et al., 2020). However, its immense potential for activating stem cell grafts remains largely unexplored. The application of optogenetics to precisely modulate stem cell graft activity in vivo presents a novel and noninvasive approach for manipulating cell behaviour following stem cell transplant after SCI. This strategy holds great promise for advancing our understanding and enhancing therapeutic interventions for SCI. Therefore, our research proposes the use of optogenetic to precisely modulate spinal cord-derived NPCs expressing the light-sensitive cation channel channelrhodopsin-2 (ChR2), under ubiquitous promoter, transplanted into an in vivo model of spinal cord injury. Our findings demonstrated that optogenetic stimulation of NPCs enhance early functional locomotor recovery following a T8 hemisection in rats by increasing graft survival, modifying graft identity and activity. Additionally, optostimulation of NPC has been shown to influence astrocyte reactivity at the lesion border, thereby improving the neuroprotective properties of stem cells. Furthermore, considering the critical role of excitatory synapsis in functional recovery after SCI (Kathe et al., 2022), we further aim to directly excite human neural stem cell (hNSC) by expressing the ChR2 under CAMKII promoter in vitro. Our results revealed that direct optogenetic stimulation effectively increase human neural stem cell activity and synchrony in cell culture, highlighting its potential as a promising strategy for further testing in a clinically relevant model of SCI. This approach holds promise for providing a more excitatory neural landscape to influencing the establishment of crucial new connections at the lesion site, thereby leading to improved locomotor function.

12:30 – 13:00 Mohammed M. Anwar

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