Developmental stage of transplanted neural progenitor cells influences anatomical and functional outcomes after spinal cord injury in mice.
Developmental stage of transplanted neural progenitor cells influences anatomical and functional outcomes after spinal cord injury in mice.
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DOI：
10.1038/s42003-023-04893-0
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发表时间：
2023-05-19
影响因子：
5.9
通讯作者：
Dulin, Jennifer N. N.
中科院分区：
文献类型：
--
作者：
Aceves, Miriam;Tucker, Ashley;Chen, Joseph;Vo, Katie;Moses, Joshua;Kumar, Prakruthi Amar;Thomas, Hannah;Miranda, Diego;Dampf, Gabrielle;Dietz, Valerie;Chang, Matthew;Lukose, Aleena;Jang, Julius;Nadella, Sneha;Gillespie, Tucker;Trevino, Christian;Buxton, Andrew;Pritchard, Anna L. L.;Green, Peyton;McCreedy, Dylan A. A.;Dulin, Jennifer N. N.
神经祖细胞（NPC）移植是替代脊髓损伤（SCI）后丢失神经元的一种有前景的治疗策略。然而，移植细胞组成如何影响宿主轴突群的再生和突触发生，或脊髓损伤后运动和感觉功能的恢复，人们知之甚少。我们将从 E11.5-E13.5 小鼠胚胎中分离出的发育受限的脊髓 NPC 移植到成年小鼠 SCI 部位，并分析移植物轴突生长、细胞组成、宿主轴突再生和行为。早期移植物表现出更大的轴突生长、腹侧脊髓中间神经元和 Z 组脊髓中间神经元的富集以及宿主 5-HT+ 轴突再生的增强。后期移植物丰富了晚生背角中间神经元亚型和 N 组脊髓中间神经元，支持更广泛的宿主 CGRP+ 轴突向内生长，并加剧了热超敏反应。任何类型的鼻咽癌移植物均不会影响运动功能。这些发现展示了脊髓移植物细胞组成在确定 SCI 后解剖和功能结果中的作用。在脊髓损伤的小鼠模型中，移植的神经祖细胞的发育阶段显示出影响脊髓损伤后的解剖和行为结果
Neural progenitor cell (NPC) transplantation is a promising therapeutic strategy for replacing lost neurons following spinal cord injury (SCI). However, how graft cellular composition influences regeneration and synaptogenesis of host axon populations, or recovery of motor and sensory functions after SCI, is poorly understood. We transplanted developmentally-restricted spinal cord NPCs, isolated from E11.5-E13.5 mouse embryos, into sites of adult mouse SCI and analyzed graft axon outgrowth, cellular composition, host axon regeneration, and behavior. Earlier-stage grafts exhibited greater axon outgrowth, enrichment for ventral spinal cord interneurons and Group-Z spinal interneurons, and enhanced host 5-HT+ axon regeneration. Later-stage grafts were enriched for late-born dorsal horn interneuronal subtypes and Group-N spinal interneurons, supported more extensive host CGRP+ axon ingrowth, and exacerbated thermal hypersensitivity. Locomotor function was not affected by any type of NPC graft. These findings showcase the role of spinal cord graft cellular composition in determining anatomical and functional outcomes following SCI. In a mouse model of spinal cord injury, the developmental stage of transplanted neural progenitor cells is shown to influence anatomical and behavioral outcomes after spinal cord injury
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影响因子：
4.2
作者：
Brock, John Hoffman;Graham, Lori;Tuszynski, Mark Henry
通讯作者：
Tuszynski, Mark Henry
影响因子：
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作者：
Bonner, Joseph F.;Blesch, Armin;Neuhuber, Birgit;Fischer, Itzhak
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通讯作者：
Tuszynski, Mark H.
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0.8
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通讯作者：
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影响因子：
2.5
作者：
BREGMAN, BS;KUNKELBAGDEN, E;ONEILL, A
通讯作者：
ONEILL, A