Péron Sophie, Droguerre Marine, Debarbieux Franck, Ballout Nissrine, Benoit-Marand Marianne, Francheteau Maureen, Brot Sébastien, Rougon Geneviève, Jaber Mohamed, Gaillard Afsaneh
INSERM U1084, Experimental and Clinical Neurosciences Laboratory, Cellular Therapies in Brain Diseases Group, University of Poitiers, 86022 Poitiers Cedex, France.
Université de Poitiers, U1084, 86073 Poitiers Cedex, France.
J Neurosci. 2017 Feb 15;37(7):1820-1834. doi: 10.1523/JNEUROSCI.2936-16.2017. Epub 2017 Jan 13.
We previously reported that embryonic motor cortical neurons transplanted immediately after lesions in the adult mouse motor cortex restored damaged motor cortical pathways. A critical barrier hindering the application of transplantation strategies for a wide range of traumatic injuries is the determination of a suitable time window for therapeutic intervention. Here, we report that a 1 week delay between the lesion and transplantation significantly enhances graft vascularization, survival, and proliferation of grafted cells. More importantly, the delay dramatically increases the density of projections developed by grafted neurons and improves functional repair and recovery as assessed by intravital dynamic imaging and behavioral tests. These findings open new avenues in cell transplantation strategies as they indicate successful brain repair may occur following delayed transplantation. Cell transplantation represents a promising therapy for cortical trauma. We previously reported that embryonic motor cortical neurons transplanted immediately after lesions in the adult mouse motor cortex restored damaged cortical pathways. A critical barrier hindering the application of transplantation strategies for a wide range of traumatic injuries is the determination of a suitable time window for therapeutic intervention. We demonstrate that a 1 week delay between the lesion and transplantation significantly enhances graft vascularization, survival, proliferation, and the density of the projections developed by grafted neurons. More importantly, the delay has a beneficial impact on functional repair and recovery. These results impact the effectiveness of transplantation strategies in a wide range of traumatic injuries for which therapeutic intervention is not immediately feasible.
我们之前报道过，成年小鼠运动皮层损伤后立即移植胚胎运动皮层神经元可修复受损的运动皮层通路。阻碍将移植策略应用于多种创伤性损伤的一个关键障碍是确定治疗干预的合适时间窗。在此，我们报道损伤与移植之间延迟1周可显著增强移植组织的血管化、移植细胞的存活及增殖。更重要的是，通过活体动态成像和行为测试评估发现，这种延迟显著增加了移植神经元形成的投射密度，并改善了功能修复和恢复。这些发现为细胞移植策略开辟了新途径，因为它们表明延迟移植后可能会实现成功的脑修复。细胞移植是一种有前景的皮质创伤治疗方法。我们之前报道过，成年小鼠运动皮层损伤后立即移植胚胎运动皮层神经元可修复受损的皮层通路。阻碍将移植策略应用于多种创伤性损伤的一个关键障碍是确定治疗干预的合适时间窗。我们证明损伤与移植之间延迟1周可显著增强移植组织的血管化、存活、增殖以及移植神经元形成的投射密度。更重要的是，这种延迟对功能修复和恢复有有益影响。这些结果影响了移植策略在多种创伤性损伤中的有效性，对于这些创伤性损伤，治疗干预并非立即可行。
