Fetal rat neural progenitor cell transplantation after spinal cord injury improves motor recovery following optogenetic stimulation

[EN] Spinal cord injury (SCI) disrupts communication between the brain and the spinal circuits, resulting in severe motor, sensory, and autonomic dysfunctions. Transplantation of neural progenitor cells (NPCs) has been demonstrated to provide multiple benefits; however, limited graft survival and ne...

Descripción completa

Detalles Bibliográficos
Autores: Sanchez-Martin, Maria del Mar, Alastrue-Agudo, Ana, López-Mocholí, Eric, Martín-Pérez, Samuel, Maninno, Lois, Fraga Sánchez, Ana Isabel, Vidal-Beneyto, Quique, Conesa, Ana, van Niekerk, Erna, Tuszynski, Mark, Moreno-Manzano, Victoria, Giraldo, Esther|||0000-0001-5488-3011, Paniagua G, Monreal-Trigo, Javier|||0000-0002-4067-1867, Terrés-Haro, José Manuel|||0000-0001-5794-7332
Tipo de recurso: artículo
Fecha de publicación:2025
País:España
Institución:Universitat Politècnica de València (UPV)
Repositorio:RiuNet. Repositorio Institucional de la Universitat Politécnica de Valéncia
Idioma:inglés
OAI Identifier:oai:dnet:riunet______::0051fb90ec8dea6a6f6dfc9a2afcd4ad
Acceso en línea:https://riunet.upv.es/handle/10251/235137
Access Level:acceso abierto
Palabra clave:Rat neural progenitors cell
Optogenetics
Spinal cord injury
Channelrhodopsin-2
Motor recovery
Human neural stem cells
03.- Garantizar una vida saludable y promover el bienestar para todos y todas en todas las edades
Descripción
Sumario:[EN] Spinal cord injury (SCI) disrupts communication between the brain and the spinal circuits, resulting in severe motor, sensory, and autonomic dysfunctions. Transplantation of neural progenitor cells (NPCs) has been demonstrated to provide multiple benefits; however, limited graft survival and neuronal differentiation must be overcome to achieve improved results. Here, we explore the optogenetic modulation of rat spinal cord-derived NPC expressing channelrhodopsin-2 (ChR2) through adeno-associated virus serotype 9-mediated transduction, transplanted into the sub-acute stage after SCI. Daily blue-light stimulation and ChR2-dependent activation control of the modified NPC significantly enhanced locomotor skills, run speed, sustained walking coordination, and body stability in a rat SCI model. Engrafted rat NPC-ChR2 reduces astrocytic reactivity and the injured area volume, preserves a higher number of descending propriospinal neurons above the injury and a higher innervation of 5-hydroxytryptamine fibers to choline acetyltransferase-positive motoneurons below the injury, and the increased vesicular glutamate transporter expression suggests an enhanced excitatory synaptic activity. Overall, sustained activation of rat NPC post-transplantation offers a promising strategy for improved locomotor recovery following SCI.